The two men were gored in the leg and another five people were taken to Pamplona hospitals with minor injuries sustained in the 8am dash today, a Navarra regional government statement said.
The gorings were caused by a lone bull that raced ahead of the pack, raising panic among the hundreds of screaming runners along the 930-yard (850-metre) course from a holding pen to Pamplona's bull ring.
The morning runs are the highlight of the nine-day street-party festival, which was immortalised in Ernest Hemingway's 1926 novel The Sun Also Rises and attracts thousands of foreign tourists.
Dozens of people are injured each year in the runs, most of them in falls. Fifteen people have died from gorings since record-keeping began in 1924.
Yesterday, an American who co-wrote a book called Fiesta: How To Survive The Bulls Of Pamplona became one of their victims after he was gored.
Bill Hillmann, a 32-year-old from Chicago and a longtime participant in the event, was gored twice in the right thigh, organisers said on their website.
The injury was serious but not life-threatening, the Navarra regional government said.
A 35-year-old Spaniard from Valencia was also in serious condition after being gored in the chest during the same run on the festival's third day, the statement said.
The day before, authorities said a 23-year-old British man from Nottingham was in serious condition with chest injuries and rib fractures
The man - identified only by his initials, TH - was hurt in the second running, along with a Japanese man and a Spaniard. One person was gored in the opening run.
The six bulls used in each run are invariably killed in afternoon bullfights in the ring.