The plane carrying Melania Trump and a pool of reporters returned to Joint Base Andrews in Maryland after 10 minutes in the air.
Reports from inside the plane said Secret Service officers hopped up from their seats and headed toward the front of the plane.
A few moments later, a thin haze of smoke could be seen. Reports say there was also a smell of something burning that grew stronger.
The members of the press were brought wet towels and told to hold them over their faces if the smell became too strong.
A crew member said the issue stemmed from "a malfunctioning comms unit" that had overheated, but the White House has not confirmed that information.
Within minutes, the smoke reportedly cleared, and the smell slowly began to dissipate.
"Minor mechanical issue," Stephanie Grisham, the first lady's Communications Director, said in a statement. "Everything is fine and everyone is safe,"
The plane landed back at Joint Base Andrews around 9 a.m. Officials say Mrs. Trump's trip was being re-evaluated, but a Health and Human Services spokesperson confirmed she would still be coming to Philadelphia.
After a new flight, Melania Trump arrived and toured a hospital's neonatal care unit to learn about the treatment given to newborns suffering from opioid withdrawal.
She spoke briefly at a conference at Thomas Jefferson University Hospital on newborns who have been exposed to opioids while in the womb. The hospital has provided care to mothers with opioid use disorder and their newborn children for more than 45 years.
She was introduced by Health and Human Services Secretary Alex Azar, who said the Trump administration's plan to fight the opioid epidemic was "comprehensive and driven by the best science we've got."
She began her remarks by saying "sorry for a little delay."
Mrs. Trump said there are few things harder than seeing a newborn suffering from opioid withdrawal, and that she wants to shine a light on the issue.
"As the caretakers of the next generation, it is our responsibility to protect our most valuable and vulnerable, our children," she said.
After touring Jefferson's neonatal care until, the first lady was also going to visit with mothers who are in addiction treatment in a program that allows them to have their children with them.
According to TV reporters traveling with the first lady, the original flight was in the air about 10 minutes when smoke filled the cabin. A member of the crew handed out damp washcloths for passengers to put over their mouths, and Secret Service agents rushed to the front of the plane.
It was not immediately clear what caused the problem on the aircraft, a Boeing C-32A identified as "Bright Star."
The visit was one of a number of stops planned to promote her "Be Best" campaign, which focuses on issues affecting children, including the importance of healthy pregnancies.
(The Associated Press contributed to this report)
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