We have previously shown that mu opioid receptors in the guinea pig ileum preparations are poor models for those in the central nervous system to study the phenomenon of opiate tolerance. Since we have shown subsequently that the mu opioid receptors in the mouse vas deferens preparation differ from those in the guinea pig ileum, we investigated the possibility that the mu receptors in the mouse vas deferens might be better models for the study of opiate tolerance. The degree of tolerance produced by incubation of mouse vas deferens preparations with morphine in vitro was relatively low. However, when mice were either implanted with morphine pellets (75 mg free base) or injected s.c. with 100, 50 or 25 mg/kg of morphine sulfate, a large magnitude of tolerance in their vasa deferentia was consistently observed. When pA2 analyses were performed in the tolerant vasa deferentia (25 mg/kg) using naloxone, the pA2 value was 7.55 +/- 0.18 compared to the control value of 8.45 +/- 0.24. Since the tissue became significantly more refractory to the effects of the opiate antagonist with the development of tolerance, which is the opposite of what happens with central mu receptors, we conclude that the mu opioid receptors in the mouse vas deferens are not adequate models for those in the central nervous system to study the phenomenon of tolerance.