OBJECTIVE A program of research was established on the question whether melatonin played a chemopreventive role in the development of foci of aberrant crypts in the intestinal tract of male rats. Male F344 rats were injected i.p. with an aqueous solution of 15 mg/kg azoxymethane (AOM) on day 50 and day 57, and a group was also injected i.p with 0.5 mg melatonin in 0.5 ml of 10% ethanol solution 5 times per week beginning at age 47 days. Foci and multiplicity of aberrant crypts were determined after 8 weeks. These groups of animals were kept in light daily from 4∶30 to 16∶30. RESULTS In the group receiving AOM and the melatonin injections, there were fewer foci of aberrant crypts in the colon and the average number of crypts was lower after 8 weeks, compared to the group on AOM alone. CONCLUSIONS Melatonin inhibited the formation of foci of aberrant crypts in the descending colon of rats. Also, it reduced the number of aberrant crypts per focus from foci with 3 and more aberrant crypts.