The inhibitory effect of selenium, 13-cis-retinoic acid, and their combination was studied in an animal model in which squamous cell carcinoma of the tongue was induced by 0.5% 9,10 dimethyl-1,2 benzanthracene (DMBA). A controlled, blinded experiment was carried out using 60 Syrian hamsters divided into four groups of 15 each. When compared to controls, the mean day of carcinoma onset was delayed 3 weeks for animals given selenium, 6 weeks for animals given retinoic acid, and 5.5 weeks for animals given selenium plus retinoic acid. The differences between each experimental group and the control group are statistically significant. We conclude that both selenium and retinoic acid inhibit the development of DMBA-induced squamous cell carcinoma of the tongue in hamsters. The dose of retinoic acid used produces a stronger inhibitory effect, but is associated with significant toxicity. At the doses used, combined inhibitory effect is no greater than that for retinoic acid alone.