We have shown earlier that naltrexone, a long acting opioid antagonist, inhibits the development and growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors. We extended these studies to determine the independent effects of naltrexone when fed at 75 mg/kg diet during the initiation (I), promotion (P), or initiation plus promotion (I+P) phases of DMBA-induced rat mammary carcinogenesis. The percentage of rats with palpable tumors as well as the number of tumors per rat were determined during the 130 day experiment. When fed during the 1, P, or I+P phases, mammary tumor incidence was significantly inhibited by 27%, 60% and 45% respectively, as compared to the control group. Similarly, tumor multiplicity was significantly reduced by naltrexone treatment. Tumor multiplicity was reduced by 40%, 73%, and 70% when fed naltrexone during I, P, and I+P respectively, as compared to the controls. These results indicate that naltrexone acts on the I and P phases, with the effects being maximal when fed during the P and I+P phases.