Central or systemic administration of agonists directed at the mu or delta opiate receptors generally produce a greater degree of analgesia in males than in females. To date, the majority of studies examining sex based differences in opioid analgesia have employed acute noxious stimuli (i.e. tail-flick and hot plate test); thus, the potential dimorphic response of centrally acting opiates in the alleviation of persistent inflammatory pain is not well established. In the present study, right hindpaw withdrawal latency (PWL) to radiant thermal stimuli was measured in intact male and cycling female Sprague-Dawley rats before and after unilateral hindpaw injection of the inflammatory agent complete Freund's adjuvant (CFA). Control animals received intraplantar injection of saline. Twenty four hours after CFA or saline injection, animals received either saline or morphine bisulfate (0.5 - 15 mg/kg; s.c.). Separate groups of control or inflamed animals were tested on their responsiveness to morphine at 7, 14 and 21 days post-CFA or saline. No sex differences were noted for baseline PWLs, and females displayed slightly less thermal hyperalgesia at 24 hrs post-CFA. At all morphine doses administered, both the antihyperalgesic effects of morphine in the inflamed animals, and the antinociceptive effects of morphine in control animals, were significantly greater in males in comparison to females. Similarly, in males, the antihyperalgesic effects of morphine increased significantly at 7-21 days post-CFA; no significant shift in morphine potency was noted for females. These studies demonstrate sex-based differences in the effects of morphine on thermal hyperalgesia in a model of persistent inflammatory pain.