Sixty-four male and female Syrian golden hamsters (Mesocricetus auratus) were divided into 4 equal groups. Group 1 animals had the posterior lateral borders of their tongues painted three times weekly with a 0.5% solution of 7,12-dimethylbenz[a]anthracene (DMBA) in acetone. Group 2 animals were painted with DMBA and also received 10 mg of 13-cis-retinoic acid in peanut oil administered orally by pipette twice weekly. Group 3 animals received only retinoid, and group 4 animals were untreated controls. Four animals in each group were killed at 12, 14, 16, and 18 weeks. In the DMBA-painted animals receiving 13-cis-retinoic acid, the leukoplakia and epidermoid carcinomas developed more slowly and were better differentiated microscopically. The better degree of differentiation was demonstrated by ultrastructural studies. Less cellular separation and fewer microvilli-like structures were evident. No tubular mitochondria were observed. Less dispersion of heterochromatin occurred throughout nuclei, and the basal lamina tended to be regular and continuous.