There is evidence in the literature to suggest that melatonin has a functional role in the iris-ciliary body (ICB). In this study we provide results which argue for the occurrence of melatonin receptors in this region of the eye. Autoradiography showed that specific binding of 125I-iodomelatonin is associated with the ICB although the resolution did not allow for discrimination of binding between the ciliary epithelium and the iris musculature. The binding of 125I-iodomelatonin to ICB homogenates is saturable with a single population of binding sites and with KD and Bmax values of 428 pM and 170 fmol (g wet weight)-1, respectively. The order of potency of various substances to compete with the 125I-iodomelatonin binding sites is chloromelatonin = melatonin > 6-OH-melatonin > N-acetylserotonin > 5-methoxytryptamine > serotonin. Neither iodomelatonin nor serotonin affected basal levels of cAMP, but both decreased the forskolin elevated cAMP levels. However, the iodomelatonin effect, unlike that of serotonin, was not antagonised by propranolol. The combined data argue for the presence of melatonin receptors in the ICB of the rabbit. These receptors are negatively linked to the stimulation of cAMP and are distinguishable from serotonin receptors.