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Washington Metropolitan Police Chief Cathy Lanier said a shooter was dead and one police officer was wounded in an "engagement" with at least one gunman.
"One shooter is deceased,'' she said. "We have multiple victims inside who are deceased. We potentially have two other shooters who have not been located."
Lanier said police are searching for a white male wearing a tan military-style uniform with short sleeves, a military beret and a hand gun. Police are also searching for a black man around 50 years old wearing an olive drab military-style uniform and carrying a long gun, Lanier said.
She said there was no evidence that the suspects were military members.
A federal law enforcement official, speaking on condition of anonymity because of the fluid nature of the investigation, said authorities were investigating the possibility of other shooters, but there was no immediate evidence of more than one assailant.
Washington Mayor Vincent Gray called the incident a "horrific tragedy" and lauded police for their quick response.
Media outlets including CBS and the Associated Press, citing the Navy, said the number of dead had risen to six. Maj. Ed Buclatin, the public affairs chief for the Navy Installations Command, earlier had tweeted "four killed and eight injured."
FLIGHTS: Airport resumes operations after Navy shooting
Janis Orlowsky, chief medical officer at MedStar Washington Hospital Center, said the hospital was treating three victims — a male D.C. police officer and two women.
She said the police officer had multiple gunshot wounds to his legs and was in surgery. One woman was shot in the shoulder, and the other in the head and hand. All are expected to survive, she said.
The hospital had been told to expect additional victims, Orlowsky said. "We're pretty darned experienced at this."
Rick Mason, a program management analyst who is a civilian for the Navy, said he was at the Navy Yard when a gunman began shooting from a fourth-floor overlook in the hallway outside his office. He said the gunman was aiming down at people in the building's cafeteria on the first floor. Mason said he could hear the shots but could not see a gunman.
Mason said overhead speakers told workers to seek shelter and later to leave the building.
Patricia Ward, a logistics management specialist, said she was in the cafeteria. "I heard three shots — pow, pow, pow. Thirty seconds later I heard four more shots."
Then panic, as people tried to get out of the cafeteria. "A lot of people were just panicking. There were no screams or anything because we were in shock."
Dave Sarr, an environmental engineer, was walking down a nearby street when he saw people running from the Navy Yard. Sarr has seen an evacuation drill a few days earlier at the Navy Yard. "At first I thought it was another drill," Sarr said. "Then I saw an officer with his weapon drawn."
President Obama made a brief statement, describing the victims as "patriots" and promising a thorough investigation. "I made it clear to my team that I want the investigation to be seamless," Obama said.
The first news broke with the Navy reporting on its Twitter feed that there was an "active shooter" at Building 197 at the Navy Yard, and that three shots had been fired at 8:20 a.m. ET. The Navy later reported deaths and injuries, but details remained fluid.
James Killingsworth, a mason from Frederick, Md., was working on rebuilding a historic wall about 100 yards from the Navy Yard entrance when he heard two gunshots. If there were any other shots, he said, they were immediately drowned out by wailing sirens.
"Everything they had, Secret Service, federal police, everyone came speeding down the street. I've never seen so many police in my life," he said. "Scary morning."
Flights at nearby Washington Reagan National Airport were disrupted, with all departures temporarily halted at the airport.
The Navy Yard is located on the banks of the Anacostia River, a few blocks from the Nationals baseball stadium. It's in an urban area where the development of new parks, shops and apartments has been ongoing.
The Washington Nationals baseball team had not determined whether Monday night's game against the Atlanta Braves would be played. A parking lot at Nationals Stadium was being used as a site for families seeking to reunite with loved ones who work at the Navy Yard.
The city had not decided how long the area by the Navy Yard, including the baseball stadium, would remain closed to the public, said Keith St. Clair, communications director for the deputy mayor for public safety and justice.
Naval Sea Systems Command is the largest of the Navy's five system commands and accounts for a quarter of the Navy's entire budget. It builds, buys and maintains the Navy's ships and submarines and their combat systems.
NAVSEA headquarters' security requires guests to pass through turnstiles that are watched by security guards before entering. Visitors must also turn in their phones and other electronic recording devices upon entry.
Capt. Michael Graham, who works at NAVSEA, was running late this morning and by the time he arrived at work the base was already in a lockdown.
Graham said he had never seen a shelter-in-place drill in his five years at NAVSEA.
"I've never seen a shelter-in-place, I've seen the normal fire drills things like that, but never a shelter-in-place drill," said Graham. "Normally the drills you have are to get out of the building."
Marine Barracks Washington also put its base on a partial lockdown, only allowing Marines to leave if they were on official business, said Capt. Jack Norton, a base spokesman. A small contingent from Marine Barracks Washington's Guard Company serves at the Navy Yard, Norton said.