The tissue distribution, course of secretion, and sex differences of morphine were delineated in Ascaris suum. Nitric oxide (NO) release in various tissues in response to morphine and its metabolite morphine-6-glucuronide (M6G) were also examined. Ascaris suum of both sexes along with their incubation fluid were analyzed for morphine concentrations by high- performance liquid chromatography (HPLC) over a 5-day period. Various tissues were also dissected for HPLC and NO analysis. Morphine was found to be most prevalent in the muscle tissue, and there is significantly more morphine in females than males, probably because of the large amounts present in the female uterus. Morphine (10⁻⁹ M) and M6G (10⁻⁹ M) stimulated the release of NO from muscles. Naloxone (10⁻⁷ M) and N-nitro-l-arginine methyl ester (10⁻⁶ M) blocked (P < 0.005) morphine-stimulated NO release from A. suum muscle tissue. d-Phe-Cys-Tyr-d-Trp-Om-Thr-Pen-Thr-NH₂ (CTOP) (10⁻⁷ M) did not block morphine's NO release. However, naloxone could not block M6G-stimulated NO release by muscles, whereas CTOP (10⁻⁷ M) blocked its release. These findings were in seeming contradiction to our earlier inability to isolate a μ opiate receptor messenger RNA by reverse transcriptase–polymerase chain reaction using a human μ primer. This suggests that a novel μ opiate receptor was possibly present and selective toward M6G.