Ukraine’s acting president Oleksandr Turchynov has warned eastern regions that they will be stepping into the abyss if they vote for self-rule.
Polls are open in the regions of Donetsk and Luhansk despite the call by Russian President Vladimir Putin for a postponement of the ballot.
According to the Ukrainian news website Obozrevatel, security services say four people have been arrested near Slovyansk carrying weapons and thousands of ballot papers marked with “yes” votes.
The EU and the US have condemned the referendums, which have no outside observers.
Organisers say a second ballot could be held on joining Russia.
People are also voting in Lukansk, where pro-Russian separatists have also seized government buildings and clashed with Ukrainian forces.
“I will vote in the referendum for the independence of Luhansk so the city’s money will stay here, not in Kyiv,” said resident Lulia Dorohova.
Many in Ukraine’s eastern regions mistrust the Kyiv authorities. But it is unclear exactly what a vote for self-rule would bring.