With half the votes counted, former Prime Minister Viktor Yanukovych led current PM Yulia Tymoshenko by 37% to 24%.
The two were on opposing sides of the Orange Revolution in 2004-5, but both now favour closer ties with Russia.
Current President Viktor Yushchenko has been eliminated from the vote.
A total of 18 candidates took part in the election.
The BBC's Gabriel Gatehouse, in Kiev, says there is much disillusionment among voters over the failure to tackle corruption and links with the EU.
It was Mr Yanukovych's victory in the 2004 election that was annulled by the Orange Revolution and brought Mr Yushchenko and Ms Tymoshenko to power.
Turnout in the election was reported to be less than 50% by early afternoon. Polls closed at 2000 (1800 GMT).
In the capital Kiev, voters walked to polling stations through light snow.
In the eastern city of Donetsk, one polling station encouraged voters with vodka and sausage.
President Yushchenko cast his ballot at a polling station in central Kiev with his wife, Kateryna, and their five children.
"Ukraine once again will demonstrate that it is a European democratic country, that it is a free nation, free people and free election," he said.
Warnings of unrest
The leading candidates have accused each other of trying to rig the election, and there have been warnings of unrest after the vote.
In an effort to boost confidence in the election, foreign observers have spread out across Ukraine to monitor voting.
Jens-Hagen Eschenbacher, of the Organisation for Security and Co-operation in Europe, said about 600 OSCE election monitors are in place, as well as thousands of other foreign observers.
The Orange Revolution led Ukrainians to expect sweeping changes - integration with Europe and an end to corruption, our correspondent says.
But the reality has not lived up to expectations and there is widespread disillusionment with politicians across the spectrum, he adds.
