The Northwest Airlines plane involved was an Airbus A320
An inquiry has begun after a US plane heading from San Diego to Minneapolis missed the airport it was meant to land at by 150 miles (240km).
Contact with the Northwest Airlines plane was lost for an hour as it flew at 37,000ft, sparking hijack fears.
The crew said they had been distracted by a "heated discussion" but officials will check if they had fallen asleep.
Flight 188, carrying 147 passengers, landed safely at Minneapolis after contact was resumed.
A statement released by the National Transportation Safety Board (NTSB) said: "The crew stated they were in a heated discussion over airline policy and lost situational awareness."
Board spokesman Keith Holloway told the Associated Press news agency that reports that the pilots may have fallen asleep were "speculative" but the investigation would look at "fatigue issues".
The plane's cockpit voice recorder and flight data recorder have been taken from the plane and are being sent to the board's laboratory in Washington, DC.
Passenger Andrea Allmon: 'The plane was swarmed by police'
Questions have been raised about how the pilots could have missed any warning signals - including city lights and cockpit displays showing that they were no longer on the right path.
The NTSB's former chief investigator into major accidents, Ben Berman said pilots learned to become instinctively aware of when they needed to start landing preparations and it would take a "fairly dramatic event" to distract them, AP reported.
The plane left San Diego at 1500 local time (2200 GMT) for what would normally be a three-hour journey.
Air traffic controllers lost radio contact with the plane approximately an hour before it was due to reach its destination of Minneapolis-St Paul International/Wold-Chamberlain Airport.
The plane missed its intended stop and continued on for a further 16 minutes before the airline managed to speak to the pilots.
The Federal Aviation Administration (FAA) contacted the military and two fighter jets were put on alert.
There were initial concerns the plane had been hijacked or had faced other problems and that was why the crew were not responding.
Northwest Airlines merged with Delta Air Lines in 2008.
In a statement, Delta Air Lines said the plane's pilot and co-pilot had been "relieved from active flying".
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It said a decision would be made about them once its own internal investigation and one by the FAA and the safety board were over.
Brent Bjorlin, who was on the flight, told the Minnesota Star Tribune newspaper that the passengers had not realised what had happened until they landed and security officials boarded the plane.
Fellow passenger Andrea Allmon said it was "unbelievable" that the pilots had allegedly not been paying attention.
"These guys are supposed to be paying attention to the flight. The safety of the passengers should be first and foremost," she said.
Doug Church, a spokesman for the National Air Traffic Controllers' Association, told the Wall Street Journal controllers at the airport began worrying about terrorism as a factor when they could not reach the crew.
He said when the controllers eventually made contact, to allay their fears the crew had been threatened or overpowered, they made the pilots prove they were still in control of the plane.
Once they were satisfied, the plane made its way back to the airport.
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