The US is activating a defence system in Romania aimed at protecting Europe from ballistic missile threats.
The system has been under development for years and is aimed against potential long-range threats from the Middle East, according to officials from the US and Nato.
But the development has angered Russia, which is opposed to having the advanced military system in such close proximity.
The US and Nato said the missile shield, which is able to track and shoot down incoming missiles, is purely defensive and powerless against Russia's large stockpile of intercontinental ballistic missiles.
US assistant secretary of state for arms control, verification and compliance, Frank Rose, said: "Russia has been building an advanced system for a long time and they do it very well. We don't have the technical capability to deal with that threat."
Russian officials have dismissed claims the planned missile shield is intended to fend off missile threats from Iran. President Vladimir Putin has pointed to the determination of the US and Nato to pursue the project after a nuclear deal with Iran as proof that it is aimed at Russia. This is something Western officials deny.
Nato deputy spokeswoman Carmen Romero said: "Ballistic missile proliferation is a growing threat. More and more countries are trying to develop or acquire ballistic missiles.
"Moreover, missile technology is becoming more sophisticated, lethal and accurate, and increasing in range.
"For us to discount or ignore that very real missile threat would be irresponsible."
Russia has also threatened to react to another planned defence site in Poland by deploying Iskander missiles to Kaliningrad, the Russian territory between Poland and Lithuania that is the most militarised zone in Europe.
The Iskanders, which can be fitted with either nuclear or conventional warheads, have a range of up to about 300 miles, putting much of Poland in reach. They were temporarily deployed to Kaliningrad during military manoeuvres last year to demonstrate Russia's quick deployment capabilities.
Polish defence officials are convinced some are still there.
Michal Baranowski, the Warsaw office director of the German Marshall Fund of the United States, an institute devoted to trans-Atlantic affairs, said: "What the Russians are protesting against are forces that are unable to threaten them.
"Their protests are disingenuous. We know - and they know - that these are defence forces that are at a level that could be easily overwhelmed."
US, Nato and Romanian officials will hold a ceremony on Thursday to mark the start of operations of the site in Deveselu, a village in southern Romania, with Nato secretary general Jens Stoltenberg due to deliver a speech.
A day later Polish and US officials will break ground at a planned site in the Polish village of Redzikowo, near the Baltic Sea. It is set to go online in 2018.
Both sites will be part of a system called the European Phased Adaptive Approach.
The system also currently includes radar in Turkey and four naval destroyers with a home port in Spain. With only interim capabilities, it is now under command of the US Navy but will be transferred to Nato once fully operational.
The programme was launched by former US president George W Bush but adapted significantly by President Barack Obama, who eliminated a component intended to be in the Czech Republic.
Ties between Russia and Nato took a sharp turn for the worse when Russia annexed Crimea in 2014 and began supporting a pro-Russian insurgency in eastern Ukraine. That led Nato to ratchet up military exercises in Central and Eastern Europe to reassure allies who fear they could be targeted next.
Nato is also discussing a plan to deploy a continuous rotation of about 4,000 troops to the Baltic states and possibly Poland to reassure nervous allies. Nato defence ministers are expected to discuss that in June, with a final decision on deployment to be taken the following month by Mr Obama and other Nato leaders at a summit in Warsaw.