US Secretary of State Hillary Clinton has overseen the signing in Poland of a key missile base agreement.
The deal sets up a permanent US missile base as part of a revamped version of the controversial missile defence shield.
Russia opposes a Polish base hosting US missiles. Mrs Clinton said the new deal did not threaten Russia.
Mrs Clinton arrived from Ukraine, which was the first stop on a tour of eastern European states.
She will later visit Azerbaijan, Armenia and Georgia.
Mrs Clinton witnessed the signing of the amendment to the ballistic missile agreement with her Polish counterpart, Radoslaw Sikorski, in the southern city of Krakow.
Mrs Clinton said the agreement would "protect Poland and our allies from evolving threats, such as those from Iran".
She added: "This is purely a defensive system. It is not directed at Russia. It does not threaten Russia."
Poland had agreed with the US administration of George W Bush to host a permanent US military base and missiles at a disused airstrip in Redzikowo near the Baltic Sea coast.
The amendment to the agreement takes into account changes brought in by President Barack Obama.
President Obama scrapped the Bush-era plans to build a major defence system in Poland and the Czech Republic.
Russia welcomed the scrapping of the Bush plan but still opposes the Poland base. Moscow recently said it did "not understand the logic and focus of US-Polish co-operation in this sphere".
Mrs Clinton said the door was still open for Russia to take part in its missile defence plans but that so far it had not "responded positively".
The BBC's Adam Easton in Warsaw says that Washington has re-evaluated the threat from countries such as Iran and designed a more flexible missile defence programme.
He says that instead of stationary interceptor rockets capable of shooting down inter-continental missiles, Poland will host from 2018 mobile launchers which can knock out attacks from any range.
Mrs Clinton also discussed Poland's shale gas deposits.
Our correspondent says that if Poland is found to have large deposits it could radically alter energy security in Europe, which currently depends heavily on Russian gas.
On her Ukraine trip, Mrs Clinton said that the door to Nato membership remained open.
Following the election of President Viktor Yanukovych, who is seen as being much more pro-Russian, the Ukrainian parliament passed a measure asserting the country's non-aligned status, effectively rejecting any ambition to join Nato.
Mrs Clinton said: "Ukraine is a sovereign and independent country that has the right to choose its own alliances and Nato's door remains open.
"But it's up to Ukraine to decide whether or not you wish to pursue that or any other course for your own security interest."
In Azerbaijan and Armenia, Mrs Clinton will push for a resolution of the region's conflicts, and bolster US access to an overland route used for supplying troops to Afghanistan, says the BBC's David Stern in Kiev.
In Georgia, Mrs Clinton will have to reassure officials that the government of embattled President Mikhail Saakashvili still has US support despite Washington's attempt to improve relations with Russia, he adds.