Oral 13-cis-retinoic acid was effective in the treatment of skin cancer, and a variety of disorders of keratinization (lamellar ichthyosis, Darier's disease, pityriasis rubra pilaris), and cystic acne. An oral synthetic aromatic derivative of retinoic acid (RO-10-9359) was similarly tested and found to be more effective and less toxic than 13-cis-retinoic acid in the treatment of the disorders of keratinization. A topical synthetic aromatic retinoid (RO-11-1430) was tested in a double-blind manner against placebo cream and found to be ineffective in the treatment of disorders of keratinization. A high initial, low maintenance dosage of 13-cis-retinoic acid was found to be a comparably effective schedule but less productive of toxicity than previously used continuous high-dosage schedules in the treatment of cystic acne. Prospective analysis of patients treated with 13-cis-retinoic acid showed small but significant elevations in plasma lipids and changes in lipoproteins. These changes returned to normal after therapy was stopped. Patients treated with RO-10-9359 had similar changes which were dose dependent and responsive to dietary management.