Police said the shooting happened on a northbound 75 bus in the 7600-block of South State Street, just off the Dan Ryan Expressway, in the Greater Grand Crossing neighborhood at about 6:17 p.m.
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According to police, there was an altercation between a 35-year-old man, and an 18-year-old man and woman on the bus. During the altercation, the 35-year-old pulled out a gun and shot the victims.
"Bullets started flying everywhere, four or five shots. And I ducked, sir, I don't know what happened," one witness said.
The 18-year-old man was struck in the chest, arm and stomach. The 18-year-old woman was struck in the underarm. Both were taken to University of Chicago Hospital where their conditions were stabilized.
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A 59-year-old man took himself to St. Bernard Hospital with a graze wound to his left side, police said.
Police said the shooting was likely recorded.
"There's video in the CTA bus we'll be looking at, are in the process of getting," said Chicago Police Sergeant Rocco Alioto. "It's high-def video that will give us an idea of what exactly transpired."
Witnesses said as the shooter fled he fired at the outside of the bus, then ran off into a neighborhood east of State Street.
Police are questioning a person of interest, and said there were multiple witnesses on the bus at the time of the shooting.
Area South detectives are investigating.