Five US states are holding primary contests, known as Super Tuesday II, for November’s presidential election, giving Democrat and Republican front-runners a chance to cement their leads.
Polls have opened in Ohio and Florida – both deemed key states – as well as in North Carolina, Illinois and Missouri.
Democratic front-runner Hillary Clinton will hope to fend off a challenge from her resurgent rival, Bernie Sanders.
Meanwhile Donald Trump will aim to edge out his Republican rivals in the race.
The New York real estate mogul is the favourite to win his party’s nomination but has run into fierce opposition from within the Republican establishment, as well as facing condemnation from the Democrats.
Mr Sanders, a Vermont senator, and Mrs Clinton, a former Secretary of State, have accused Mr Trump of encouraging his supporters to beat up protesters, after violence broke out at a planned appearance by Mr Trump in Chicago.
Meanwhile, Republican candidate Marco Rubio, currently in third place, has said he must win in his home state of Florida in order to stop Mr Trump from “hijacking” his party’s nomination.
Ohio Governor John Kasich is also aiming for a win in his home state in order to obstruct Mr Trump’s progress to the nomination.
Victories for any of Mr Trump’s rivals – Mr Rubio, Mr Kasich, or Senator Ted Cruz of Texas – would give hope to the Republicans fighting to block him.