The present study investigated the question of how restraint affects the hypothalamo-pituitary adrenocortical axis and the hypothalamo-pituitary gonadal axis in intact, adult female rhesus macaques in both the follicular and luteal phases of the menstrual cycle. Restraint was chosen because it is not physically harmful to the animal but rather serves primarily as a psychological stressor. Blood samples were collected from a remote site at 15-min intervals beginning at 0700 h from tethered adult female rhesus macaques. Each animal was subjected to 6 h of chair restraint after a 3-h control period in the animal's home cage. Samples were collected for an additional 6 h after the end of the restraint period, when each animal was returned to its home cage. Brief anesthesia with ketamine (administered through indwelling catheter) facilitated transfer of the animals to and from the chair. Blood samples were also collected from undisturbed females in both the follicular and luteal phases to document LH, cortisol, and progesterone secretion throughout the day. Plasma ACTH and cortisol, measured as indices of stress, were elevated within 15 min after initiation of restraint and remained elevated after the animals were returned to their cages. In animals sampled in the follicular phase, mean plasma LH levels were lower during restraint and remained suppressed for several hours after the animals were removed from restraint. LH levels were not significantly inhibited by restraint in the luteal phase. When the opiate receptor antagonist naloxone (Nx; 5 mg bolus plus 5 mg/h) was given beginning 2 h after the initiation of restraint, LH levels were elevated compared to prerestraint levels in both phases of the menstrual cycle. These data indicate that restraint is a potent activator of the pituitary-adrenal axis and that at least in the follicular phase of the menstrual cycle, restraint inhibits pituitary LH release. This inhibition of gonadotropin release may involve endogenous opiate suppression of GnRH release, since Nx reversed the effect of restraint.