Melatonin administration to pituitary-grafted male and female rats resulted in a marked decrease of previously high plasma prolactin levels, while an increase in prolactin levels was observed in sham-operated controls. The latter effect was significant only in males. Treatment with melatonin did not modify basal LH hormone levels or LH responses to luteinizing hormone-releasing hormone (LHRH) in sham-operated rats of either sex. However, in pituitary-grafted females, melatonin increased both basal and LHRH-stimulated LH levels towards values recorded in sham-operated controls. No effects on basal LH levels were detected in grafted males under melatonin treatment, but the response of LH to LHRH was markedly increased and no longer differed from the values measured in sham-operated control animals pretreated with saline. Melatonin did not affect follicle stimulating hormone (FSH) levels except for an increase in FSH response to LHRH in grafted females. These findings suggest the existence of sex-dependent effects of melatonin on LH and FSH secretions. These effects of melatonin may be mediated by the different plasma prolactin levels in pituitary-grafted and sham-operated rats.