Mr Biden has set criteria for accepting missile defence
Senator Joe Biden, the chairman of the Senate Foreign Relations Committee, told the BBC he believed they would have the votes to block the plans if the Bush administration failed in its current diplomatic efforts to win acceptance for the system.
"I'm hopeful I can convince the majority of my colleagues... that it matters a great deal how the administration pursues missile defence and what it pursues," he said.
Mr Biden has also said he will lead a congressional delegation to China, Taiwan and South Korea to discuss missile defence and non-proliferation.
He is expected to meet Chinese President Jiang Zemin and other regional leaders on his 4-11 August trip.
He said that it was vital for the US to get relations with the region's countries right.
Criteria
BBC Washington correspondent Jon Leyne says that as one of the most influential figures in the Senate, Mr Biden is a key player President Bush must convince if missile defence is to go ahead.
Now the senator has laid out his own criteria.
Mr Bush has said in the past that he would pursue missile defence regardless of Russian or Chinese opposition.
But Mr Biden said if negotiations with Russia broke down, if there was no agreement with America's allies and strong opposition from China there would be good reason to obstruct the plan.
If in those circumstances the president still gave formal notice of America's intention to withdraw from the Anti-Ballistic Missile Treaty, then Mr Biden believed the Senate would prevent the president from getting the money to build the system.
However, if there was agreement with Russia, and good faith attempts to negotiate with North Korea and China, then he would not try to block missile defence from going forward.
Senator Biden's comments add an extra importance to the current efforts by the Bush administration to win international acceptance, or at least tolerance of its missile defence plans.
Critics will argue that Mr Biden is allowing the Russians veto over America's defences, or at the very least increasing the strength of Russia's negotiating positions.