Three people have been gored during the first bull run at the annual San Fermín festival in Pamplona.
Officials say those with gore injuries are two US citizens, aged 23 and 46, and a Spaniard.
Two others were taken to hospital with head injuries and a total of 48 others were treated by the Red Cross.
Further runs will take place every morning through the northern Spanish city’s narrow streets until next Sunday.
Those taking part, most dressed in white with red scarves, packed into the 850m (2790ft) course – which leads downhill to the town’s bull ring.
Six bulls are released daily, along with steers, before later facing professional matadors in public bull fights.
Injuries at the event are common and at least 16 people have died taking part since 1910, when records began.
The last person to die at the festival, Daniel Jimeno Romero, was gored in the neck in 2009 during the fourth run of the festival.
A 46-year-old Californian man gored in the neck on Sunday required surgery, the Associated Press reports.
The other injured American is reportedly a 23-year-old from Kentucky, who was gored in the thigh along with a 40-year-old Spanish man.
The festival attracts thousands of revellers from around the world.
It also involves religious processions, parties and concerts and was depicted in the 1926 Ernest Hemingway novel The Sun Also Rises.
Bull fighting and running is regularly criticised by animal rights activists. On Friday, they demonstrated on Pamplona’s streets – dressed in horns and lying down with fake spears in their backs.
Anyone over 18 can take part in the runs, but most participants tend to be men.
A high-profile gang rape at the 2016 festival prompted nationwide protests and an ongoing review of rape laws in Spain.