Scuffles broke out between pro and anti-Donald Trump groups as the Republican presumptive presidential nominee held a rally in a city near the Mexican border, along which he has pledged to build a wall if nominated.
Dispersing a protest outside the venue where Trump was speaking, police fired pepper spray. The initially peaceful gathering was deemed illegal when the crowd's behaviour became "unlawful", the San Diego police department said on Twitter.
Waving US and Mexican flags, more than 1,000 people had turned out for anti-Trump rallies in San Diego, a city on the US-Mexico border whose San Ysidro port of entry sees nearly 300,000 people a day cross legally between the countries.
San Diego is considered a binational city by many who live and work on opposite sides of the border, and about a third of the city's population is Latino.
During Trump's speech on Friday, some protesters outside the convention center scaled a barrier and lobbed water bottles at police. One man was pulled off the wall and arrested as others were surrounded by fellow protesters and backed away from the confrontation.
After the convention center emptied, clusters of Trump supporters and anti-Trump demonstrators began to mix in the streets, many exchanging shouted epithets and some throwing water bottles at one another.
At least 35 people were arrested and 18 others were left needing medical attention before calm was restored, according to police.
"I am opposed to the hateful, bigoted, racist language of Donald Trump and his arrogance and intolerance," one protester, Martha McPhail, told the local City News Service (CNS).
Riley Hansen, a 19-year-old Trump supporter who was selling T-shirts bearing his image, said it was time the US voted for a leader with a business background.
"My dad always told me you need a businessman as president," he told CNS. "I like his policies."
He has promised to build a wall along the US-Mexico border and deport the nearly 11 million undocumented immigrants who live in the US.
Shortly before taking the stage, Trump issued a statement ruling out a one-on-one debate with second-place Democratic hopeful Bernie Sanders, who was also in California, killing off a potentially high-ratings television spectacle.
The suggested debate, an idea first raised during a talk show appearance by the New York billionaire, would have sidelined likely Democratic nominee Hillary Clinton but given Sanders a huge platform ahead of the California Democratic primary.
A day after saying he would welcome a Sanders debate, Trump called the idea "inappropriate," declaring that he should only face the Democrats' final choice.
"I will wait to debate the first-place finisher in the Democratic Party, probably Crooked Hillary Clinton," Trump said in a statement.
Trump has won 1,238 delegates, one more than needed to win the Republican nomination, according to an Associated Press news agency tally on Thursday.
Friday was not the first time Trump has been greeted by protests in California, which is home to the largest Latino population in the country. Late last month, a visit to the California Republican convention set off days of protests in the area, leading to several arrests.