To investigate the role of the adrenal glands in the acute inhibition of gonadotropins induced by CRH in the primate, we have compared the effects of CRH infusion on LH and FSH before and after adrenalectomy and under variable glucocorticoid backgrounds. The studies were performed in four ovariectomized rhesus monkeys. Confirming previous observations, a 5-h iv CRH (rat/human CRH, 100-150 micrograms/h), but not saline, infusion inhibited both LH and FSH secretion. Saline and CRH infusions were repeated at random intervals after adrenalectomy under each of three different glucocorticoid backgrounds, achieved by varying the glucocorticoid replacement therapy (groups 1-3). At the time of the saline or CRH tests, mean cortisol concentrations were 38.5 +/- 6.3 (+/- SE) micrograms/dl before adrenalectomy, and 21.9 +/- 1.4, 14.3 +/- 1.1, and less than 1.0 micrograms/dl in groups 1, 2, and 3 of adrenalectomized (ADX) monkeys. In response to CRH infusion, gonadotropin concentrations significantly decreased in groups 2 and 3, but not in group 1 ADX monkeys which had the highest cortisol background. By hour 5 of CRH infusion, the percentages of the preinfusion baseline area under the curves for LH were 96.8 +/- 6.2%, 44.6 +/- 3.7%, and 53.5 +/- 6.1%, for groups 1, 2, and 3; by hour 4 the values for FSH were 95.7 +/- 3.5%, 76.2 +/- 4.7%, and 74.7 +/- 4.0% for groups 1-3, respectively. The absence of a response to CRH in group 1 animals occurred even though mean cortisol concentrations were lower than those in the same monkeys before ADX. Morphine (9 mg, iv), which had previously been shown to decrease LH and FSH concentrations in ovariectomized monkeys, also significantly decreased LH and FSH concentrations in ADX monkeys of group 1, which did not respond to CRH. The maximal decline occurred by hour 3 after morphine injection, when LH and FSH areas under the curve were 51.5 +/- 11.4% and 61.0 +/- 3.2% of the preinfusion baseline. Our results clearly indicate that in the primate the adrenal glands are not required for the acute CRH inhibitory effect on LH and FSH, and consequently, the decrease in gonadotropins that follows CRH is not mediated by the resultant increase in cortisol release, but, rather, by central mechanisms. The results also show that the effectiveness of CRH in inhibiting gonadotropins in the ADX monkey is affected by the amount of glucocorticoids present at the time of the test; unexpectedly, the ADX monkey is more sensitive to this protective effect of glucocorticoids than the non-ADX animal.