Chemopreventive effects of orally administered Nigella sativa oil on the induction and development of 1,2-dimethylhydrazine-induced aberrant crypt foci (ACF), putative preneoplastic lesions for colon cancer, were investigated in Fischer 344 rats. Starting at 6 wk of age, 45 male rats (groups 1-3) were subcutaneously injected with DMH once a week for 3 wk. Group 1 (15 rats) served as a carcinogen control group without N. sativa administration. Group 2 or 3 (15 rats each) were given the oil in the postinitiation stage or in the initiation stage, respectively. Animals of group 4 (11 rats) were injected with 0.9% saline and received N. sativa oil from the beginning until the termination. At sacrifice, 14 wk after the start, the total numbers of ACF as well as those with at least four crypts were significantly reduced in group 2 (P < 0.01). However, treatment with N. sativa oil in the initiation stage (group 3) did not exhibit significant inhibitory effects except on foci with only one aberrant crypt. Immunohistochemical analysis of 5-bromo-2'.-deoxyuridine labeling in colonic crypts revealed the N. sativa oil to have significant antiproliferative activity in both initiation and postinitiation stages and especially in the latter. Histological examination revealed no pathological changes in the liver, kidneys, spleen, or other organs of rats treated with N. sativa. In addition, biochemical parameters of blood and urine as well as body weight gain were not affected. These findings demonstrate that the volatile oil of N. sativa has the ability to inhibit colon carcinogenesis of rats in the postinitiation stage, with no evident adverse side effects, and that the inhibition may be associated, in part, with suppression of cell proliferation in the colonic mucosa.