An anti-Syrian MP was among at least 10 people killed in an explosion in Beirut's waterfront area.
The powerful blast occurred near Beirut's popular beachfront
Walid Eido died in the blast, in the mainly Muslim Manara neighbourhood, officials said.
Mr Eido is the third member of Lebanon's anti-Syria parliamentary majority to be killed in a bombing in the past two years.
President George W Bush condemned the bomb attack, in which at least 10 other people were wounded.
A number of other high-profile anti-Syrian figures have been killed in Lebanon since 2005.
In a statement the White House said there had been a "clear pattern of assassinations" in recent years of those opposed to Syrian interference in Lebanon's affairs.
President Bush did not blame Syria for the attack directly but warned that "efforts by Damascus and Tehran to foment instability in Lebanon must stop now".
The latest blast comes two weeks after the UN Security Council voted to set up a tribunal to try suspects in the death of former Lebanese Prime Minister Rafik Hariri, killed in a car bombing in Beirut two years ago.
Damascus denied any role in that attack.
Lebanon's Future TV said Mr Eido, who was in his 60s, was killed along with one of his sons and two of his bodyguards.
Mr Eido was a member of the Future Movement of Mr Hariri's son, Saad.
Smoke and debris
The explosion occurred at 1730 (1430 GMT) in a side street between two popular beach resorts, the Long Beach and the Sporting Club.
Television pictures from the scene showed wreckage strewn across a wide area.
Feb 2005: Former PM Rafik Hariri
June 2005: Anti-Syria journalist Samir Kassir
June 2005: Ex-Communist leader George Hawi
Dec 2005: Anti-Syria MP Gebran Tueni
Nov 2006: Industry Minister Pierre Gemayel
June 2007: Anti-Syria MP Walid Eido
The smouldering, upturned remains of at least one vehicle could be seen amid chunks of debris and shattered glass from surrounding buildings.
The BBC's Kim Ghattas in Beirut says there was chaos as rescue workers and fire trucks tried to get to the area.
Telecommunications Minister Marwan Hamadeh blamed Syria for the attack, saying it was trying to wipe out the anti-Syrian majority in parliament.
"It is the same serial killer who wants to liquidate the parliamentary majority; it is a physical liquidation by the Syrian regime," Mr Hamadeh told the AFP news agency.
After the resignation last week of another coalition member, Mr Eido's death leaves the anti-Syrian bloc with a slim majority of just three members in parliament.
Wednesday's blast was the sixth explosion in just four weeks in Lebanon. Two people were killed in the previous blasts.