The importance of opiate receptors outside the central nervous system for the inhibitory actions of morphine on male rat sexual behavior was evaluated. Morphine (10 mg/kg) produced an almost complete inhibition of sexual behavior. This inhibition was antagonized by naloxone at a dose of 1 mg/kg but not at a dose of 0.25 mg/kg. The quaternary opioid antagonist methylnaloxone effectively blocked the inhibitory actions of morphine at a dose of 20 mg/kg but not at a dose of 5 mg/kg. Since the affinity of methylnaloxone for opiate receptors is about 5% of that of naloxone, it may be concluded that both antagonists were about equally effective in inhibiting the effects of morphine. Furthermore, the opiate-like drug loperamide was found to inhibit sexual behavior. This drug acts mainly outside the central nervous system. Its effect was blocked by both naloxone and methylnaloxone, suggesting that opiate receptors are involved. It was also shown that methylnaloxone is unable to block the reinforcing effects of morphine in the conditioned place preference procedure. Because the reinforcing effects of opiates seem to be localized to the central nervous system, it may be proposed that methylnaloxone does not antagonize morphine's central effects. Moreover, loperamide had no effect in the place preference procedure, suggesting that this drug does not act at central opioid receptors. Taken together, these data show that peripheral opioid receptors are responsible for at least some of the inhibitory actions of morphine on male sexual behavior. After treatment with morphine + methylnaloxone, ejaculatory mechanisms were facilitated, reflected in a reduced number of preejaculatory intromissions and a shortened ejaculation latency.(ABSTRACT TRUNCATED AT 250 WORDS)