Voters are going to the polls in the marginal seat of Corby, knowing their choice will be closely scrutinised as an indicator of the state of national politics.
The by-election was prompted by the resignation of Conservative MP Louise Mensch earlier this year.
The high-profile backbencher stepped down because she felt unable to balance the demands of representing her constituency with her family life.
She moved to New York to be with her husband, Peter, who is a rock promoter.
Labour held the seat before the last election but it was won by the Tories in 2010 with a slim majority of just under 2,000.
Corby has traditionally swung between the two main parties.
The constituency is divided between the mainly Labour-supporting town of Corby itself, and outlying villages in which the Conservative vote is particularly strong.
With Labour enjoying substantial leads in national opinion polls, the by-election is viewed as a key test of whether Ed Miliband's troops can translate that nominal supremacy into actual votes at the ballot box.
It would be no surprise if the third-place Liberal Democrat vote is squeezed, as so often happens in by-elections.
The key test for Nick Clegg's party may be to ensure their vote does not slip behind one or more of the many minority and fringe candidates who are contesting the seat.
By-elections are also being held in Manchester Central and Cardiff South and Penarth, after the MPs in both seats stood down to run in the Police and Crime Commissioner elections.