Ten women with endometriosis were treated with medroxyprogesterone acetate (MPA), 150 mg intramuscularly every second week. After 2 weeks, there was a significant (8%) decrease in the high-density lipoprotein (HDL) concentration. This reduction became more pronounced after 8 and 24 weeks' medication. The HDL reduction was confined to the HDL2 subfraction, which was decreased by 15%, 33%, and 58% after 2, 8, and 24 weeks, respectively; there was no significant change in the HDL3 concentration. During treatment, there was a continuous increase in the mean MPA plasma level and a strong inverse correlation between this level and the mean HDL and HDL2 cholesterol concentrations. It was concluded that MPA affects HDL metabolism in a dose-dependent way and in the same direction as other progestins.