Single biweekly injections of melatonin were administered to lizards (Sceloporus occidentalis) free-running (exhibiting their endogenous circadian activity rhythm) in constant dim illumination. The injections caused phase shifts in the activity rhythm whose magnitude and direction were a function of the time of the melatonin injections, relative to activity onsets. Plotting the direction and amount of phase shift versus the time (phase) at which the injection was given generates a phase-response curve (PRC). The PRC shows that injections administered between midsubjective day and early subjective night (6-15 hr after activity onset) elicit phase advances in the activity rhythm, whereas injections given at other phases of the activity cycle induce phase delays. The existence of a PRC for melatonin suggests that the daily endogenous rhythm of melatonin (i.e., of pineal origin) may be involved in phasing, or entraining, the circadian system of lizards. The shape of the PRC also allows predictions as to the effects of continuous exogenous melatonin administration on the period of free-running activity rhythms as well as on the mechanism of entrainment of activity rhythms to daily melatonin injections.