We evaluated 72 clinical Neisseria gonorrhoeae isolates for in vitro susceptibility to cocaine hydrochloride and its metabolite benzoylecgonine and to penicillin, tetracycline, erythromycin, ceftriaxone, and ofloxacin. Although there was a wide range of susceptibilities to the antimicrobial agents, cocaine and its major metabolite, benzoylecgonine, had no demonstrable antigonococcal activity. Cocaine use is frequently associated with outbreaks of sexually transmitted disease. We hypothesized that the dramatically decreasing incidence of gonorrhea over the past 15 years may be in part due to pharmacological effects of cocaine. However, since cocaine and its metabolite have no in vitro antigonococcal activity, this hypothesis is unlikely.