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7 year oldPresident Donald Trump said Mr Pruitt had done "an outstanding job, and I will always be thankful to him".
But Mr Pruitt has been embroiled in allegations of ethics violations for months.
His deputy Andrew Wheeler will take over as acting head of the agency, Mr Trump said.
The long list of Scott Pruitt controversies<p> Artistic director collects award at Paris fashion week while rumour mill suggests Gucci, Burberry or Margiela move</p>