Effects of melatonin and N-acetylserotonin on the cyclic AMP (cAMP) concentration in the organ-cultured rat thyroid gland were investigated. Exposure of the thyroid explants to melatonin (10(-8) M) resulted in a decrease of cAMP levels. Melatonin at higher concentrations (10(-7) M and/or 10(-6) M) failed to influence the thyroid cAMP level. N-acetylserotonin (10(-6) M), like melatonin in the lowest concentration employed, reduced cAMP concentrations in the thyroid explants when compared with controls. Unexpectedly, melatonin (at a concentration of 10(-7) M) added to the incubation medium with TSH (60 mU/ml), decreased the cAMP concentration in the thyroid compared with the group exposed to melatonin (10(-7) M) alone.