Seattle police think the stabbing occurred on the bus, but no one reported seeing a knife.
Police weren't commenting on a motive, but at least one witness, who said he was sitting about five to seven feet from the fight, reported hearing the 48-year-old man use a racial epithet before the stabbing.
The confrontation began about 2:30 p.m. on a No. 14 bus as it traveled north on Third Avenue en route to Capitol Hill.
"I got on the bus at Third and James," said Matthew Griffin, 26, "and there was a fairly tall, skinny white guy ... making comments, rambling on."
Then that man used a slur, Griffin said. A black man got up, and a fight ensued, he said.
Scott Moss, Seattle police spokesman, said the 48-year-old man's friend broke up the fight. Those two walked off the bus at the next stop, between Marion and Madison streets.
Griffin said there was a rush for the doors, and the other in the fight got out, as well. "I don't think anyone was panicked," he said. "I just think people wanted to get out the way."
Police described the man they are looking for as black, about 5 feet 10, between 200 and 220 pounds, with a salt-and-pepper-colored goatee. He appeared to be in his late 40s or early 50s.
Meanwhile, the 48-year-old man walked a short distance before he collapsed on the street. His friend then discovered the stab wound, Moss said.
Paramedics arrived within minutes and took the injured man to Harborview Medical Center in Seattle. He either died en route or at the hospital. No one else was injured.
Authorities last night had not released the dead man's name. Police weren't sure where he lived.
The veteran driver, who has worked for Metro for 24 years, noticed the commotion but wasn't aware of what was happening, said Linda Thielke, Metro spokeswoman.
Every seat was taken, and people were standing in the aisles, she said. The fight occurred near the middle of the bus.
A video camera was operating on the bus, but technicians weren't able to provide useful evidence to police because a "protective cover" on the camera blocked its view of the incident, Thielke said.
It was the first homicide on a Metro bus since Nov. 27, 1998, when passenger Silas Cool shot the driver, then himself, causing the bus to go over the side of the Aurora Bridge.
Four months ago the Metropolitan King County Council approved a Metro Transit policy to increase police presence aboard buses and at bus stops.
The number of assaults on Metro bus passengers rose from 46 in the first six months of last year to 56 in the same period this year. Assaults on drivers dropped from 36 to 34.
Anyone with information is asked to call the Seattle police homicide unit at 206-684-5550.