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None of the injured were gored by a bull but fell while running through the narrow, twisting cobbled streets of the old town of the city pursued by the bulls, a spokesperson for the festival said.
The two Spanish nationals were aged 21 and 31, she added. The ages of the Scot and the American were not given.
About 2000 people took part in the bull run, which lasted two and a half minutes and was described by organisers as "fast and clean".
San Fermin, Spain's most famous festival, attracts tourists from all over the world. It began Monday and ends on July 14.
From Tuesday and each day of the festival thereafter, six bulls are released at 8am to run from their corral over an 825-metre course to the bullring where they face matadors in the afternoon.
Fourteen people have been killed since 1911 in the bull run, which is broadcast live on Spanish television.
The festival also features a range of concerts, street parties, dances and — in some cases — excessive drinking.
AFP