The effect of constant light exposure on 2-[125I]iodomelatonin binding sites in the guinea pig spleen was investigated. Guinea pigs exposed to constant light for 2-3 weeks showed an increase in the number of splenic 2-[125I]iodomelatonin binding sites, without any difference in the binding affinity, in comparison to animals kept under 12 h light/12 h darkness condition, whereas the splenic indices were similar in both groups. This light dependence of the splenic 2-[125I]iodomelatonin binding sites suggests that the binding sites are melatonin receptors and that the light dependent immunomodulatory effect of melatonin is mediated via a direct action on the lymphoid tissue.