South Korea agreed in April to reopen what was formerly the third-largest overseas market for U.S. beef. It had been shut for most of the past 4 1/2 years following the first U.S. case of mad cow disease in a Canadian-born cow in Washington state in 2003.
That deal, coupled with some sensational media reports, sparked fears of mad cow disease and triggered protests calling for scrapping or renegotiating the agreement.
"Dictator Lee Myung-bak," read signs waved at the protest, far larger than previous rallies, which have reached up to 10,000 people.
"If we are anti-American, you are anti-Korean," read another, a swipe at the pro-American president who has vowed to strengthen ties with the U.S.
Students, labor union members, office workers were among those who filled the plaza, which was surrounded by special buses used by riot police.
The rally was largely peaceful, with most protesters dispersing voluntarily.
Earlier in the day, however, about 60 activists staged a protest in front of the presidential office and were taken away for questioning, police said.
Anger has intensified since Thursday, when the government announced it would implement the April 18 agreement with Washington and resume beef imports within days despite widespread public opposition.
The beef issue has emerged as the biggest domestic challenge for Lee's fledgling administration.
Though his margin of victory in December's election was the largest ever in South Korea, his handling of the beef agreement has seen his popularity plummet to levels near 20 percent.
The timing of the deal - just hours before a summit with President Bush at his Camp David retreat - struck a particularly raw nerve.
Protesters claim Lee was too quick to concede to U.S. demands for access to South Korea's market to win favor with Washington and garner support in Congress for ratification of a separate free trade agreement.
Lee's office said it had no comment on the rally.
Government ministers have repeatedly tried to calm public fears about mad cow disease. Lee even went on national television to apologize for not sufficiently consulting with the public on the beef issue.
On Friday, South Korea's political opposition asked the Constitutional Court to block U.S. beef imports, saying the government's policy on the American meat violates the people's right to health.
Scientists believe mad cow disease, or bovine spongiform encephalopathy, spreads when farmers feed cattle recycled meat and bones from infected animals. The U.S. banned recycled feeds in 1997.
In humans, eating meat products contaminated with the cattle disease is linked to variant Creutzfeldt-Jakob disease, a rare and fatal malady.
