Using gonadally-intact female cats, we showed previously that estrogen, applied topically to the spinal cord, attenuated the exercise pressor reflex. Although the mechanism by which estrogen exerted its attenuating effect is unknown, this steroid hormone has been shown to influence spinal opioid pathways, which in turn have been implicated in the regulation of the exercise pressor reflex. These findings prompted us to test the hypothesis that opioids mediate the attenuating effect of estrogen on the exercise pressor reflex in both gonadally-intact female and ovariectomized cats. We therefore applied 200 µl of 17- estradiol (0.01 µg/ml) with and without the addition of 1000 µg naloxone, a µ- and - opioid antagonist, to a spinal well covering the L₆-S₁ spinal cord in decerebrated female cats that were either gonadally-intact or ovariectomized. The exercise pressor reflex was evoked by electrical stimulation of the L₇ or S₁ ventral root, a maneuver which caused the hindlimb muscles to contract statically. We found that in gonadally intact cats the attenuating effect of estrogen was more pronounced than that in ovariectomized cats. We also found that in gonadally-intact female cats, naloxone partly reversed the attenuation of the pressor response to static contraction caused by spinal estrogen application. For example, in intact cats the pressor response to contraction before estrogen application averaged 39 ± 4 mmHg (n=11), whereas the pressor response 60 minutes afterwards averaged only 18 ± 4 mmHg (P<0.05). In contrast, the pressor response to contraction before estrogen and naloxone application averaged 33 ± 5 mmHg (n=11), whereas afterwards it averaged 27 ± 6 mmHg (P<0.05). In ovariectomized cats naloxone was less effective in reversing the attenuating effect of estrogen on the exercise pressor reflex.