The attack also shut down a street and forced the evacuation of several businesses while beekeepers removed the hive, which was estimated to contain 60,000 bees.
The trouble started at a storage yard when a man in a wheelchair apparently disturbed the hive, causing the bees to bombard him, Santa Ana fire Capt. Steven Snyder said.
"He was attacked and stung over 60 times and had fallen out of the wheelchair and was yelling for help," Snyder said.
The man's cries attracted the attention of three bystanders who ran to his aid.
The bees were so aggressive that the three men had to retreat initially, but they dove back in and managed to pull the man to safety, Snyder said.
The men were stung dozens of times during the "very impressive" rescue, he said.
"They probably saved his life," Snyder said.
All four men had difficulty breathing and suffered rashes, nausea and vomiting. They were taken to hospitals and at least two of the men were released Thursday night, Snyder said.
He didn't know their conditions or if the man in the wheelchair was still hospitalized. No names were released, but Snyder estimated all four men were in their 40s.
Two firefighters who responded to the scene also were stung.
Snyder said DNA tests were planned to determine if the bees were Africanized because of their aggressive behavior.
The bee attack wasn't the first to make headlines this week.
On Wednesday, Africanized bees swarmed several farm animals and killed a 1,000-pound hog at a farm in Bisbee, Ariz. An 800-pound pregnant sow also was stung so many times that it went into a coma and lost its litter.
In northern Arizona, a 49-year-old man remained hospitalized after authorities say he disturbed bees nesting under a cattle trough Sunday and was stung more than 1,000 times.