This study examined whether chronic cocaine exposure could reduce reproductive fitness of adult male mice by interfering with their production of the puberty-accelerating pheromone, an androgen-dependent urinary pheromone that accelerates puberty in juvenile female mice. Administered at a high dose of 60 mg/kg body weight/day, cocaine caused mortality, body weight loss, and suppression of circulating testosterone during the first week of treatment. However, at 40 mg/kg/day, it resulted in little adverse effect on these parameters. Animals showed habituation to repeated cocaine exposure by regaining part of the lost weight and reelevating suppressed testosterone level at later stages of treatment. Urine samples collected from animals receiving 60 mg/kg cocaine daly for 2 weeks lost the puberty-accelerating effect. However, neither a 3-day treatment of the same dose nor a lower dose of 40 mg/kg reduced the effectiveness. The diminished effect of cocaine-treated male mouse urine might reflect lowered testosterone levels with a lag of 10 to 15 days, similar to that of castrated male mouse urine. These results indicate that cocaine has no direct effect on the production of priming pheromone, and its metabolites in the urine did not affect the response of juvenile females to the pheromone.