The effects of two enkephalinase inhibitors, SCH 34826 and phospho-leu-phe, on male rat sexual behavior and conditioned place preference were evaluated. SCH 34826, administered intraperitoneally, reduced the ejaculation latency to both the first and second ejaculation at a dose of 30 mg/kg. This dose also reduced the first postejaculatory interval. No other effect was obtained with this drug. Phospho-leu-phe, administered intracerebroventricularly, increased mount and intromission latency at doses of 50 and 100 micrograms. A dose of 25 micrograms reduced the latency to the first ejaculation as well as the number of preejaculatory intromissions. The postejaculatory interval was also reduced at this dose. SCH 34826, 100 and 30 mg/kg, and phospho-leu-phe, 25 micrograms, had no effect in the conditioned place preference procedure. These observations seem to suggest that there is no functionally relevant tonic release of enkephalins. Therefore, the effects obtained on sexual behavior may indicate that enkephalins are released before and during the course of sexual activity. The function of such a release could be to facilitate ejaculatory mechanisms in the way found in the present studies. Previous work has shown that ejaculation-induced reward is opioid dependent, further supporting the hypothesis of opioid release during sexual activity. Taken together, these data suggest an important role for opioids, probably enkephalins, in the physiological control of sexual behavior.