We have previously observed that gonadal steroid treatments, which stimulate a proestrous-like LH surge in ovariectomized rats, cause a marked reduction in the responsiveness to opiates of a variety of CNS processes. The present study was undertaken to determine if a similar decline in opiate responses is associated with the endogenous steroid-induced LH surge on the afternoon of proestrous. Rats were evaluated for thermic, nociceptive, behavioral and LH secretory responses to morphine sulfate on diestrous I afternoon (DiPM) and proestrous morning (ProAM), times at which LH secretion is low, as well as on proestrous afternoon (ProPM) during the preovulatory LH surge. While on DiPM and ProAM, morphine caused a 33–45% reduction in serum LH levels at doses as low as 5 mg/kg b.w., in ProPM rats doses as high as 10 mg/kg did not affect LH secretion. Similarly, ProAM rats showed a prompt and sustained analgesic response to morphine, but ProPM rats showed a delayed response of shorter duration. DiPM rats showed an acute response intermediate to that of ProAM and ProPM animals. While DiPM and ProAM rats exhibited the expected hypothermic response to a high dose of morphine (15 mg/kg), ProPM rats showed no decline in core body temperature, but exhibited a delayed hyperthermic response to the opiate. DiPM and ProAM rats showed a dose-dependent decline in locomotor behavior in response to morphine. In contrast, ProPM rats, which exhibited a significantly elevated basal locomotor activity, failed to show a reduction in locomotion after morphine treatment. Collectively, these data indicate that a generalized alteration in opiate responsiveness occurs on the afternoon of proestrus. This change in CNS opiate-receptor mechanisms may play a role in the plethora of physiologic alterations which accompany the preovulatory LH surge on proestru