The possibility of interactions between the effects of cyclosporine (CyA) and prolactin to regulate various physiological functions has been suggested. To further analyze these interactions, the effect of chronic CyA administration on the secretion of adenohypophyseal hormones in hyperprolactinemic male rats, was studied. Male rats were grafted one pituitary gland under the kidney capsule or were sham-operated at 30 days of age. Both pituitary-grafted and sham-operated rats were given s.c. injections of vehicle or CyA (5mg/kg/day) for 30 days beginning on the day of surgery. Pituitary-grafting increased the plasma leveles of prolactin and decreased the plasma levels of luteinizing hormone (LH), whereas growth hormone (GH), thyroid stimulating hormone (TSH) and follicle stimulating hormone (FSH) did not change. CyA treatment to sham-operated rats did not modify plasma prolactin levels and decreased plasma levels of GH and LH. Administration of the immunosuppressor to pituitary-grafted rats decreased plasma prolactin levels and augmented plasma levels of LH and FSH. Plasma TSH levels did not change after CyA treatment either in sham-operated or in pituitary-grafted rats. These data suggest that CyA may modify the effects induced by prolactin on pituitary hormone secretion, although direct effects of the drug on the hypothalamic-pituitary axis cannot be excluded, according to the data obtained in sham-operated rats.