The aim of this project was to evaluate the effect of retinyl acetate (RA), melatonin (Mel) and their combination on N-methyl-N-nitrosourea (NMU)-induced rat mammary carcinogenesis. Female Sprague-Dawley rats were given two intraperitoneal doses of NMU, each of 50 mg/kg of b.w. between 43rd to 57th postnatal day. The administration of RA started 11 days and the administration of Mel 12 days before the first dose of NMU. RA was given daily in a dose of 8.2 mg per animal and day at the base of the tongue. Mel was given as a solution (20 micrograms/ml of tap water) between 3 p.m. and 8 a.m., from 8 a.m. to 3 p.m. the animals were drinking tap water only. The experiment was finished 22 weeks after the first administration of the carcinogen. The tumour incidence in the control group was 88%, in the group treated with RA 80% and in the group treated with Mel 61%. A substantial decrease in tumour incidence to 37% was noted in the group treated with RA plus Mel. Significant differences in incidence were noted in the group treated with the combination of RA and Mel as compared to the control group and the group treated with RA. Chemoprevention lengthened the latency significantly in the group treated with Mel and with the combination of RA and Mel. The decrease in tumour frequency per group was confirmed in the group treated with the combination of RA and Mel; differences between groups in the frequency per tumour-bearing animal were not observed. The volume of mammary tumours in the groups treated with chemopreventive agents was not changed.