The purpose of this study was to evaluate the effects of the gonadal hormones on the opioid receptor protein levels of Freund's adjuvant-treated (arthritic) male and female Lewis rats. Following a paw pressure nociception assay, the midbrain and spinal cord tissues were collected for comparison of mu, delta, and kappa opioid receptor protein levels. The effects of Freund's adjuvant-induced hyperalgesia resulted in significantly decreased nociception thresholds in both males and females, compared to vehicle treated animals in the paw pressure test. It was hypothesized that the presence or lack thereof of gonadal hormones would alter nociception, an effect temporally correlated with a change in opioid receptor protein expression. Nociceptive thresholds were altered by arthritis in both sexes, but not further altered by gonadal changes in males. A small, but significant increase in threshold was shown in ovariectomized females. In spite of the small gonadal-induced changes in the nociceptive threshold sensitivity to pressure, significant changes in the plasticity of the opioid system were observed. There was a significant increase in kappa opioid receptor protein levels in the spinal cord of arthritic ovariectomized females. Mu opioid receptor and kappa opioid receptor protein levels in the spinal cord tissue of non-arthritic male rats were significantly higher than in arthritic rats, a difference eliminated by gonadectomy. Gonadectomy produced similar results in the mu opioid receptor protein level in the male midbrain tissue as well. Sex differences were observed in both the mu and kappa opioid receptor protein levels. The spinal cord tissue of male rats, regardless of the presence of gonads or arthritis displayed significantly greater levels of mu opioid receptor protein levels than females. The removal of gonadal hormones appears to have opposite effects in males and females in terms of opioid receptor proteins, but not nociception as quantified by the paw pressure test. The role of changes in the plasticity of the opioid systems in response to arthritis or gonadal hormones remains to be elucidated.