Candidates bidding for their party’s ticket in the November US presidential election face their biggest test yet in the so-called Super Tuesday primaries.
Twelve states cast votes for candidates from either the Republican or Democratic parties or both in a contest seen as make-or-break for the hopefuls.
Contests stretch from Vermont in the east to Texas and Georgia in the south.
After earlier votes in four states, Donald Trump leads the Republican field and Hillary Clinton the Democratic.
The first polls opened in Virginia at 06:00 local time (11:00 GMT).
Senator Ted Cruz cannot afford to lose to Mr Trump in Texas, Mr Cruz’s home state, while a reverse for Mr Trump in Massachusetts, with its moderate voters, could break the property tycoon’s nationwide momentum.
Mrs Clinton is hoping to build on her weekend victory in South Carolina, where she polled heavily among African-Americans, to restore her political fortunes after a bruising defeat in New Hampshire to Bernie Sanders, her self-styled democratic socialist rival.
On November 8, America is due to elect a successor to Barack Obama, a Democratic president standing down after two terms in office which have seen the Republicans take control of both houses of Congress.
Opinion polls give Mr Trump a lead in almost all of the 11 states holding Republican contests on Tuesday: Alabama, Arkansas, Georgia, Massachusetts, Oklahoma, Tennessee, Texas, Vermont, Virginia, Alaska and Minnesota.
The colourful campaign of the billionaire, who won three of the four early voting states, has divided Republicans.
On the eve of the polls, Nebraska Senator Ben Sasse became the highest-ranked elected party member to come out and say he would not back him for president.
“I was frustrated and saddened” and would look for a third option if Mr Trump won the Republican nomination,” he said.
Marco Rubio, the third-placed Republican contender after Mr Trump and Mr Cruz, is hoping to stay competitive, gambling on a win in his home state of Florida on March 15.
Mr Trump’s commitment to several controversial immigration pledges, including the wholesale deportation of illegal immigrants and construction of a wall along the US-Mexico border, was called into question on Monday after reports describing an off-the-record conversation with the New York Times editorial board.
Mr Cruz, Mr Rubio and former Republican candidate Mitt Romney have called on Mr Trump to authorise the release of the transcript, in which Mr Trump reportedly says his hardline immigration policies would be flexible if he were elected.
“Apparently there is a secret tape that the New York Times editorial board has of Donald Trump saying that he doesn’t believe what he’s saying on immigration… I call on Donald: ask the New York Times to release the tape and do so today before the Super Tuesday primary, “Mr Cruz said.
Andrew Rosenthal, the editor of the Times editorial page, said he would not comment on an off-the-record conversation without Mr Trump’s permission.
“If [Trump] wants to call up and ask us to release this transcript, he’s free to do that and then we can decide what we would do,” Mr Rosenthal said.
Mr Trump has faced heavy criticism ahead of the Super Tuesday primaries over his failure to disavow David Duke, a Ku Klux Klan white supremacist leader who endorsed the Republican candidate.
Protesters, including some from the Black Lives Matter movement, repeatedly disrupted a Trump rally in Radford, Virginia, on Monday after his refusal to condemn Mr Duke.
Democrats are voting in Alabama, Arkansas, Georgia, Massachusetts, Oklahoma, Tennessee, Texas, Vermont, Virginia, Colorado and Minnesota, as well as in the US territory of American Samoa. Democrats abroad will also submit their votes.
Mrs Clinton is eyeing black voters in places like Alabama, Georgia and Virginia after taking eight out of ten votes in South Carolina..
Jane Sanders said her husband faced a rough map on Super Tuesday but would take his campaign through to July’s Democratic convention.
“We expect to win some states and lose some states tomorrow and we think it will only get better as it goes along,” she said.