The aim of this work was to study the effects of progesterone on the expression of high density lipoprotein binding sites by cultured human skin fibroblasts. At concentrations ranging between 10(-6)- and 10(-4) M the hormone showed a dose-dependent induction of the HDL binding sites. The effect was maximal at 48 h. The increased HDL binding was only due to an up-regulation of binding sites, without changes of the apparent Kd. This effect was not related to changes of cellular cholesterol content, and was not affected by inhibition of protein synthesis. These data suggest that the expression of binding sites for HDL can be modulated via a mechanism that does not depend upon cellular cholesterol content.