A large body of evidence has shown that ethanol inhibits the cell growth and cell proliferation in a variety of cell types. However, it has not been studied whether ethanol inhibits the proliferation of mesangial cells (MC) in the kidney. We examined the effects of ethanol on cell proliferation in cultured rat MC. Treatment with ethanol (10-200 mM) for 48 hr inhibited [(3)H]thymidine incorporation into MC in a concentration-dependent manner. The same concentrations of ethanol also inhibited the increase in cell number of MC. GF109203X and chelerythrine chloride, inhibitors for protein kinase C, eliminated the inhibitory effects of ethanol; and protein kinase C activator, PMA, mimicked the effects of ethanol. In contrast, neither the protein kinase A inhibitor H-89 nor the protein kinase G inhibitor KT5823 had any effect. These findings suggest that ethanol has inhibitory effects on the proliferation of MC, probably via activation of the protein kinase C pathway.