Modifications in prolactin and insulin specific binding in the mouse liver induced by repeated administrations of ovine prolactin (oPRL) or indomethacin were studied. oPRL induced a dose-dependent and reversible increase of prolactin binding capacity. No change was observed in dissociation constant values. Conversely, insulin binding capacity to the same liver membranes was not modified by the treatment with oPRL. The increase in the binding induced by oPRL was not influenced by cycloheximide and it is therefore not dependent on protein synthesis. On the other hand, indomethacin caused a dose-dependent inhibition of prolactin binding capacity, without changes in dissociation constant values. The inhibitory effect was specific since at the doses used insulin binding to the same membranes was not affected. When indomethacin treatment was associated to oPRL administration it was able to counteract the increase in binding capacity caused by oPRL, even at doses ineffective in reducing the binding in non oPRL-treated mice. Our results suggest that drug-induced membrane modifications can selectively affect prolactin receptors and could consequently modify the ability of the target cell to respond to different physiological or pharmacological situations.