Five women were shot by a gunman who opened fire at Northside Hospital Medical Centre in Atlanta, before he escaped the area.
Atlanta Police Chief Darin Schierbaum told reporters that a 39-year-old woman was pronounced dead at the scene.
The four injured victims were also women, aged 25, 29, 56 and 71.
Three people remain in a critical condition following a shooting at a medical building in Midtown Atlanta, police said.
Dr. Robert Jansen, Grady Health System’s Chief Medical Officer, said the other patient is still in the emergency department.
He revealed: "We were anticipating up to 12 patients. "Fortunately we only received four but we were completely prepared for it."
According to the Atlanta Police Department, the alleged suspect Deion Patterson, 24, became enraged during a trip to the medical building with his mum before allegedly opening fire.
Mr Patterson's mum is currently assisting with the police, CNN said.
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Atlanta police said there had been no additional shots fired since the initial shooting unfolded inside a Northside Medical building on West Peachtree Street in a commercial area with many office towers and high-rise apartments.
Cops said the alleged gunman currently remains at large - with police warning people to stay away from the "armed and dangerous" individual.
Police lifted the 'shelter in place' advice at 3pm EDT and said that they "have no information indicating the suspect is still in the area".
Authorities also put out a photo of Mr Patterson showing his face and asked anyone with information about his whereabouts to call 911 and not approach him.
Crime Stoppers was offering a reward of up to $10,000 for information leading to the arrest and indictment of the suspect.
Atlanta police said they are aware of a carjacking that happened not long after the shooting a few blocks away.
They said the vehicle has been recovered in suburban Cobb County, and they were working to determine whether the vehicle was connected to the shooting.
Dozens of police and fire vehicles were gathered along West Peachtree Street, as officers with assault-style rifles, helmets and vests continued to arrive more than an hour after the shooting.
The suspected alleged gunman, who was seen wearing a hoodie, had a mask over his face, in photos released by police.
Multiple emergency crews are at the scene with people being evacuated from the area.
Workers are in lockdown at nearby buildings and have been told to stay inside while the alleged gun is on the run, according social media posts.
In a statement on Twitter, cops said: "APD is investigating an active shooter in the area of 1110 W Peachtree St NW. Please shelter in place, or stay out of the area.
"We are working an active shooter situation inside a building on West. Peachtree St, between 12th St and 13th St. We are aware of multiple people injured. No suspect is in custody.
"Anyone in the area is asked to secure their building and shelter in place. Anyone not in the area is asked to stay away."
Mayor Andre Dickens tweeted he was working closely with authorities to help assist with the active shooter situation.
He wrote: "I am in close contact with the Atlanta Police Department as they are responding to the active shooting situation in Midtown near 1100 W Peachtree. Those in the area should shelter in place."
The healthcare company said it was assisting police during its investigation.
It said: "Northside Hospital is cooperating with law enforcement following the shooting at our midtown Atlanta location earlier this afternoon.
"We urge people in the area to shelter in place and follow instructions from law enforcement on the scene."
Atlanta Public Schools announced that nearby campuses have been put on lockdown while police search for the suspect.
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