US Secretary of State Condoleezza Rice arrived in Moscow on Friday for crucial talks with Russian leaders on missile defence and other disputes that have sent Cold War chills through their relations.
Rice and US Defence Secretary Robert Gates are due to meet President Vladimir Putin and then discuss the thorny issues in a combined meeting with their respective Russian counterparts, Sergei Lavrov and Anatoly Serdyukov.
Washington says the anti-missile system would protect against "rogue states" such as Iran and wants to build a radar tracking base in the Czech Republic and deploy interceptor missiles in Poland.
Moscow sees the system as a threat to its own security and has warned it would create a "new Berlin wall," with President Vladimir Putin suggesting siting it in Azerbaijan instead.
The Kremlin has also threatened to re-deploy nuclear missiles if Washington forges ahead with the project.
During her two days in Moscow, Rice will hold separate talks with Foreign Minister Lavrov, with whom she is known to have a somewhat frosty relationship.
As well as Iran, she is likely to raise the issue of the Middle East peace summit the United States is hoping to host, possibly next month.