Twenty men with nodulocystic acne were treated with oral isotretinoin (13-cis-retinoic acid) for four months. Plasma lipids and lipoprotein determinations were obtained before and during treatment to quantitate the effects of oral isotretinoin on lipid metabolism. Maximum isotretinoin-induced elevations in plasma triglyceride and cholesterol levels were 67% and 16%, respectively. Additional maximal changes included very-low-density lipoprotein cholesterol increases of 56%, low-density lipoprotein cholesterol increases of 22%, and high-density lipoprotein decreases of 10% from pretreatment values. Chronic increases in plasma cholesterol levels, increases in low-density lipoprotein cholesterol levels, and decreases in high-density lipoprotein cholesterol levels may predispose subjects to premature atherosclerosis. Because of the potential for unmasking an occult lipid or lipoprotein disorder, the plasma lipid and lipoprotein profiles of subjects receiving isotretinoin should be carefully monitored.