Studies were undertaken to evaluate the effects of chronic hyperprolactinemia (HYP) induced by the MtTW15 tumor on the thermoregulatory response of female rats to blockade of opiate receptors with naloxone. Both chronic administration of morphine and HYP cause a mild hyperthermia as evidenced by a 0.8-1.0° C elevation in rectal temperature (T(r)). Naloxone-precipitated morphine withdrawal caused a prompt increase (4.9 ± 0.76°C) in tail skin temperature (TST) and a subsequent decline in T(r)(-2.8° C). Similarly, naloxone administered to HYP rats caused a dramatic TST response which was coincident with the onset of severe HYP. This effect of naloxone was maximal at 7 weeks of tumor growth when a TST response of 4.8 ± 0.3°C was observed but was not evident prior to or 1 week following tumor inoculation, when serum prolactin levels were low. The TST response to naloxone in chronic HYP exhibited distinct pulses with an amplitude of 3.4 ± 0.4°C and a frequency of 2.2 ± 0.5 pulses per 120 min. It appears that blockade of opiate receptors in HYP rats induces instability in the regulation of skin temperature as evident by recurrent episodes of TST surges. These effects of chronic HYP on the TST response to naloxone were not influenced by ovariectomy, suggesting that changes in ovarian secretions were not involved in the response. At 4 weeks of tumor growth, immunoreactive β-endorphin concentrations in the medial basal hypothalamus, preoptic area-anterior hypothalamus and the neurointermediate lobe of the pituitary were decreased by 59, 28 and 47%, respectively. Anterior pituitary concentrations of immunoreactive β-endorphin were not significantly alltered at this time. Collectively, these data indicate that (1) HYP can induce alterations in core body temperature and skin temperature responses to naloxone which are similar to those observed in morhine-dependent rats; (2) chronic HYP causes depletion of immunoreactive β-endorphin in the hypothalamus and the neurointermediate lobe of the pituitary, and (3) chronic HYP max exert these effects by an action on β-endorphin containing neurons.