Secretary of State Colin L. Powell demanded on Sunday that Iran halt its quest for weapons of mass destruction and that Syria cease supporting terrorism.
He also called on Israeli and Palestinian leaders to take serious steps toward a peace agreement.
In a strong speech to a pro-Israel lobby group, Powell reaffirmed the Bush administration's determination to oust Iraqi President Saddam Hussein.
"We will keep his weapons of mass destruction from the Middle East," Powell said to strong applause from thousands of American Jews attending an evening session opening the American Israel Public Affairs Committee's 44th annual policy conference.
"Let there be no doubt of the outcome," he said. "We will drive Saddam Hussein and his regime from power."
Turning to Iran -- which President Bush has denounced as a member of an "axis of evil" along with Iraq and North Korea -- Powell said it must stop its support of terrorism against Israel and "must stop its pursuit of weapons of mass destruction and the ability to produce them."
Following up on an accusation last week by Secretary of Defense Donald H. Rumsfeld that Syria is allowing military equipment to flow into Iraq, Powell said, "Syria faces a critical choice" -- whether to "continue its direct support for terrorism in the dying days" of the Iraqi government.
Rumsfeld has called Syria's actions "hostile," and Powell kept up the pressure with a warning that "Syria bears a responsibility for its choices and consequences."
On the Israeli-Palestinian front, Powell renewed Bush's support for a Palestinian state and said, "Israel's security requires peace with its neighbors."
Powell also renewed Bush's call for a halt to settlement activity in the West Bank and Gaza Strip, which drew a mixed response of mild applause and a few boos.
Without mentioning the Palestinians specifically, Powell got a standing ovation when he declared that there must be "an end of violence as a political tool" against Israel.