The effects of cyclosporine (CyA) on pituitary hormone secretion in animals with previously high plasma prolactin levels have been studied. Hyperprolactinemia was either induced in 30 day old male rats by the transplantation of one anterior pituitary gland from a litter mate donor or they were sham-operated to be used as controls. Both pituitary-grafted and sham-operated animals were injected s.c. with the vehicle or CyA (5 mg/kg weight per day) for 10 days, beginning 30 days after surgery. As expected, pituitary grafting markedly increased plasma prolactin levels as compared with the values found in control animals. Hyperprolactinemia was associated with reduced plasma LH and GH levels, increased plasma TSH levels and with no changes in circulating FSH levels. CyA administration to control animals increased plasma prolactin and TSH levels, decreased plasma levels of LH and did not modify circulating values of FSH and GH. Furthermore, CyA administration to pituitary-grafted animals decreased plasma prolactin and TSH levels, whereas plasma concentrations of GH and gonadotropins did not change. These data suggest that CyA differentially affect the release of pituitary hormones and that there is an interrelationship between previously high plasma prolactin levels and CyA to modulate pituitary hormone secretion.