The gonads of male hamsters exposed to short photoperiod (LD, 10:14) or treated with melatonin in the late afternoon under long photoperiod (LD, 14:10) had undergone complete regression by the end of the treatments (8 weeks). Animals treated for the same period of time with prazosin (a putative melatonin analogue) under the same conditions failed to show a difference in their gonadal status as compared to the long photoperiod controls. Prazosin was unable to prevent melatonin-induced gonadal atrophy when injected either in the morning or 30 min before melatonin. Moreover, prazosin was without any effect on (and unable to prevent the melatonin-stimulated) progesterone production by rat adrenals under in vitro conditions. These data demonstrate that prazosin, which reportedly inhibits 2-[125I]iodomelatonin binding in the hamster brain in an affinity-related manner, does not possess properties of a biological melatonin analogue under conditions of two different model systems in two species.