Male heroin addicts or patients maintained on methadone have lower serum testosterone and luteinizing hormone than normals. The effects of a single injection of morphine (20 mg/kg) on serum testosterone levels were examined in the male rat. Within 2 h after the morphine injection, testosterone levels were significantly lower than control levels. The decline in testosterone levels reached a maximum 4 h after the administration of morphine, at which time testosterone levels were reduced by more than 85% with respect to controls. The ability of a large number of narcotics to depress serum testosterone levels, 4 h after their administration, was also examined. All narcotics depressed testosterone levels significantly and their potency relative to morphine was comparable to that observed in several other preparations, such as the guinea-pig ileum and mouse vas deferens. The testosterone-depleting effects of the narcotics appear to represent specific narcotic effects since the (-)-isomers of the narcotics were considerably more potent than the (+)-isomers, naloxone competitively inhibited the effects of morphine on testosterone levels and tolerance developed to the testosterone-depleting effects of these drugs. Acute treatment with morphine also lowered serum luteinizing hormone levels, and this reduction preceded the fall in testosterone levels by 1-2 h.