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Crowds assembled along the 70-mile route that snaked from the family's compound in Hyannis Port to the John F. Kennedy Library and Museum, where his body lay in repose. As many as 12,000 people waited in line to file past his closed casket and mark the end of a national political chapter that was equal parts triumph and tragedy.
Kennedy's widow, Vicki, who greeted well-wishers filing past the casket, said the outpouring was deeply moving for the family.
"I just want to thank them so much for coming this evening and showing love and support for my husband," she said. "It's a tremendous solace to all our family."
For many, it was hard to untangle Kennedy's larger-than-life role as statesman from his role as neighbor and local celebrity, whether he was taking a turn conducting the Boston Pops or throwing out the first pitch for the Red Sox.
"It was Teddy's home team. It just seemed appropriate to leave him the cap," said James Jenner, 28, placing a Sox cap he was wearing near the entrance to the library. "It symbolizes everything that he loved about his home state and everything he was outside the Senate."
The motorcade started in Hyannis Port, at the Cape Cod home where Kennedy's family held a private Mass. Eighty-five relatives traveled in the motorcade. They passed several sites that were significant to the senator, including St. Stephen's Church, where his mother, Rose, was baptized and her funeral Mass celebrated, and a Boston park he helped create that was named for his mother.
Among those making the trip were Kennedy's nieces Caroline, daughter of former President John F. Kennedy, and Maria Shriver, daughter of his late sister Eunice; and his son Patrick Kennedy, a Rhode Island congressman.
Mourners crowded the end of the barricaded road leading to the family compound before the motorcade departed.
Virginia Cain, 54, said she walked 2 miles from her summer home in Centerville so she could watch the procession and witness history.
"I can remember where I was when President Kennedy died, and I'll remember where I was when the senator left Hyannis Port," she said.
A bouquet of white and yellow lilies lay on the lawn of David Nylin's vacation rental near the Kennedy home, where a U.S. flag flew at half-staff in Kennedy's honor. Nylin, 38, said people had been stopping near his house to leave flowers since Kennedy died late Tuesday.
"The Kennedys and Hyannis and the Cape, they just kind of go hand in hand," he said.
On Main Street in downtown Hyannis, flags, flowers and personal notes lay at the base of a flagpole outside the John F. Kennedy Museum, where about two dozen people gathered.
Someone had placed an old Kennedy campaign sign with a new inscription: "God bless Ted, the last was first," referring to his ascension to political greatness after his two older brothers were assassinated.
Several enlarged photos showed events in Kennedy's life - meeting with Martin Luther King Jr., reading to a school girl. A rosary hung over a picture of Kennedy standing in his office. Echoes of the Kennedy history were hard to miss as the motorcade traveled through the city.
Vicki Kennedy put her hand over her heart as the procession passed St. Stephen's. A crowd that had gathered there applauded, and niece Caroline and other family members acknowledged them with a wave from their cars.
"When a member of the Kennedy family passes, it's like family. It feels like family," said Jeanne Pagano, 54, who was on the sidewalk outside the church. "I really loved the man and the family. I loved them."
The motorcade also crossed the Rose Fitzgerald Kennedy Greenway, a park created by the Big Dig highway project, which Kennedy helped shepherd through the Senate. It paused at Faneuil Hall, where the historic bell rang 47 times - once for each of Kennedy's years in the Senate.
The procession also passed the Massachusetts Statehouse - with it life-size statue of John F. Kennedy, accessible to tourists Thursday for the first time since just after the Sept. 11 attacks - and a nearby building where Kennedy opened his first office as an assistant district attorney and where John Kennedy lived while running for Congress in 1946.
After passing the John F. Kennedy Federal Building in the city's Government Center complex, the motorcade headed to the library, where Kennedy's body will remain until his Saturday funeral.
Scott Howe, 46, and his 15-year-old son, Austin, from Laurel, Md., were among those gathering outside the library.
"He seemed to really care about his constituents," Scott Howe said. "The Kennedy family - despite the money they had, had a big streak of altruism."
The family planned an invitation-only private memorial service for Friday evening at the library.
All the living presidents were expected to attend the funeral Mass on Saturday at Our Lady of Perpetual Help Basilica - commonly known as the Mission Church - in Boston's working-class Mission Hill neighborhood. President Barack Obama is scheduled to deliver the eulogy.
Shortly before the Mass, 44 sitting senators and 10 former senators will be among a group of about 100 dignitaries who will pay their respects to Kennedy at the library before making their way to the church.
Included in the group is former Sen. Birch Bayh of Indiana, who pulled Kennedy from the wreckage of a small plane that crashed near Springfield, Mass., in June 1964. The pilot and a legislative aide were killed, and Kennedy suffered a broken back that caused him pain the rest of his life.
"The Impossible Dream," Kennedy's favorite song, from the musical "Man of La Mancha," will be played at one of the services, according to the person familiar with the arrangements.
The city may soon have one more Kennedy landmark. Planning is already under way for a building to house a new Edward M. Kennedy Institute for the Senate.
Kennedy will be buried Saturday evening near his assassinated brothers - former President Kennedy and former Sen. Robert F. Kennedy - at Arlington National Cemetery in northern Virginia.
Associated Press writers Ray Henry in Hyannis Port and Denise Lavoie, Jeannie Nuss and Russell Contreras in Boston contributed to this report.