Isotretinoin (13-cis-retinoic acid) was compared with the aromatic retinoid, etretinate, in patients with severe nodulocystic acne. Evaluation of fifty-six such men receiving 1 mg/kg of one or the other of these two drugs was performed with regard to clinical improvement and change in sebum production. Lesion counting demonstrated a significant improvement in patients receiving isotretinoin, particularly in facial lesions. There was significantly less improvement with etretinate. Similarly, isotretinoin produced a marked suppression of sebum production. There was little effect of etretinate on sebum production. Side effects were limited primarily to the skin and mucous membranes.