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Reports say two gunmen involved in the shooting near Pittsburgh killed four women and one man in a residential neighborhood in Wilkinsburg, about 8 miles (13 km) east of the city.
Police and paramedics, who rushed to the scene of late Wednesday shooting, say the suspects are at large.
"I heard at least 20 shots," a witness told a local broadcaster which reported that at least two gunmen were involved.
Other regional media said seven or eight people were shot.
Police were not immediately available for comment. Several reporters in the area Tweeted photographs of ambulances and police cars, Reuters said.
Dozens of shell casings littered the pavement of an alleyway at the scene, media reports said.
Wilkinsburg is a borough of about 16,000 people, with many lower- and middle-income residents, demographic data showed.
The motive for the shooting is not known yet.
According to the US Centers for Disease Control and Prevention (CDC), more than 1.5 million domestic gun deaths were registered in the US between 1968 and 2014.
CDC also reports that firearms kill more than 33,000 people in the US every year- - a number that includes accidental discharge, murder and suicides.
Today, it is estimated that there are between 270 million and 300 million guns in the US, about one per person, according to the New York Daily News.