An explosion rocked the Geha Bridge near Tel Aviv, killing four Israelis and wounding approximately 15 others.
"We believe that this was a terror attack," Yossi Sedbon, Tel Aviv district police commander told Israel's Channel 2 television.
The blast struck a busy bus stop under the bridge, which is a major junction for commuters.
Channel Two reported rescue workers had trouble reaching the scene because of heavy rush-hour traffic.
It is unclear whether the explosive device was planted or carried by a suicide bomber.
Witnesses reported seeing police chasing two people seen fleeing the bomb site, according to the Israeli daily Haaretz.
Defense Minister Shaul Mofaz immediately ordered the Israel Defense Forces to impose a full closure on the territories.
Two of the dead were Israeli women. A fourth body is suspected to be that of the suicide bomber.
The Popular Front for the Liberation of Palestine claimed responsibility in a call to the Associated Press.
If confirmed as a suicide bombing, the attack marks the first since the Oct. 4 bombing in the northern Israeli city of Haifa which killed 21 people. WorldNetDaily reported a 29-year-old female Palestinian suicide bomber struck a crowded restaurant co-owned by Arabs and Jews as families sat down for lunch on the Jewish sabbath .
The Haifa bombing prompted Israel to launch an airstrike on a purported Palestinian terrorist-training camp inside Syria.
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