The effects of melatonin on experimental tumors so far described in the literature are contradictory. This may partially be due to negligence of the importance of environmental photoperiodic conditions and to the time of day of administration. In order to test whether the effect of melatonin on day of administration. In order to test whether the effect of melatonin on tumor growth is dependent on the photoperiod and the time of day of administration, the present experiments were carried out. It appears that under long photoperiods melatonin shows opposite effects on fibrosarcoma ascites and Ehrlich solid tumors depending on the time of the day at which the compound was administered. Tumor are stimulated by melatonin injections in the morning and inhibited by late afternoon injections. Experiments under L:D=12:12 and L:D=8:16 do not show such pronounced antagonistic effects. These results support our hypothesis that the effect of melatonin on tumor growth is dependent on the photoperiod and the time of day of administration. Possible mechanisms involved in these effects are discussed.