US Health Secretary Tom Price has resigned over the use of expensive private planes for official business.
He previously apologised after making 26 private flights since May at a cost of $US400,000 ($NZ555,000) to taxpayers.
Government officials, except those dealing with national security matters, are required to take commercial flights for work related travel.
A White House statement said President Trump had accepted Mr Price's resignation.
The statement said Mr Trump had designated Don J Wright as acting health secretary.
An investigation by the political news website Politico found that Mr Price's travels had cost more than $US1 million ($NZ1.39m).
The figure includes the cost of military aircraft used for Mr Price's trips abroad, and his use of private jets for domestic flights, Politico added.
President Trump had earlier said he was "not happy" with the expense.
Hours before Mr Price's resignation he told White House reporters: "He's a very fine man. We're going to make a decision sometime tonight. He's a very, very fine man."
Three other members of Mr Trump's cabinet are under scrutiny for their use of private planes while on the job:
* Interior Secretary Ryan Zinke flew from Las Vegas to Montana last June on a private jet that cost taxpayers more than $US12,000, according to Politico and the Washington Post
*Treasury Secretary Steven Mnuchin is accused of flying with his wife to view last month's solar eclipse
* Environmental Protection Agency chief Scott Pruitt has spent more than $US58,000 on non-commercial travel
Mr Price's departure is the latest in a string of high-profile White House resignations and firings since Donald Trump took office.
Chief strategist Steve Bannon, communications directors Anthony Scaramucci and Mike Dubke, chief of staff Reince Priebus, press secretary Sean Spicer, FBI director James Comey and national security adviser Michael Flynn have all left the administration.