Minoxidil was found to inhibit the proliferation of smooth muscle cells in the proliferating phase, but not in the quiescent phase. Treatment of proliferating or quiescent cells with minoxidil resulted in a dose- and time-dependent stimulation of elastin synthesis specifically. Maximum stimulation (fourfold) occurred in cells treated with 1 mM minoxidil for 48 h. The stimulation of elastin synthesis was accompanied by a proportional increase in elastin mRNA level, and it was partially prevented by a K⁺ channel blocker (tetraethylammonium) and completely prevented by high K⁺ salt (0.1 M). Minoxidil had no significant effect on the extent of prolyl hydroxylation in newly synthesized elastin. These results indicate that minoxidil stimulates elastin synthesis at a pretranslational level by a mechanism unrelated to cell proliferation but one that may involve K⁺ efflux. As a pharmacological agent capable of stimulating elastin expression, minoxidil would be a useful drug for the treatment of abnormal elastin metabolism.