US presidential candidates face their biggest test so far in the so-called Super Tuesday primary.
Twelve states vote for candidates from the Republican or Democratic parties, or both in a contest that is seen as a variable or a breakthrough for hope.
Racing stretches from Vermont in the east to Texas and Georgia in the south.
After earlier votes in four states, Donald Trump led the Republican field and Hillary Clinton the Democratic.
The first polls opened in Virginia at 6 a.m. local time.
Senator Ted Cruz could not afford to lose to Donald Trump in Texas, his home state, while the opposite for Trump in Massachusetts, with his moderate voters, could disrupt the national dynamics of the property tycoon.
Democratic nominee Hillary Clinton hopes to build on her weekend victory in South Carolina, where she is polling intensively among African Americans to regain her political wealth after a heavy defeat in New Hampshire by Bernie Sanders, her self-elected Democratic Socialist supporter.
On Nov. 8, America must elect a successor to Barack Obama, a Democrat president who resigned after two terms after Republicans took control of both houses of Congress.