We recently demonstrated that chronic daily administration of a superactive GnRH analog to intact rats resulted in an initial stimulation of serum LH levels with a subsequent return of LH levels to baseline at a time when testosterone levels were markedly decreased. These data demonstrated pituitary desensitization following chronic GnRH analog treatment. Administration of GnRH analog with a dose of testosterone which did not markedly lower serum LH levels when administered alone prevented the stimulation of LH secretion by analog. The present studies were undertaken to determine the effects of GnRH analog and testosterone administration on the regulation of pituitary GnRH receptors. Pituitary GnRH receptor binding was increased by analog treatment alone at 20 days and returned to control levels at 40 and 60 days of treatment in parallel to the observed changes in serum LH, demonstrating that one mechanism by which chronic GnRH analog treatment leads to pituitary desensitization is down-regulation of pituitary GnRH receptors. Testosterone administration alone decreased pituitary GnRH receptor binding. Combined GnRH analog and testosterone administration prevented the increase in pituitary GnRH receptors observed with analog administration alone. These studies demonstrate that change in pituitary GnRH receptor binding correlate with changes in serum LH and that the stimulatory effects of analog administration on LH are sensitive to inhibition by small doses of testosterone.