In an ongoing cooperative study of uncomplicated genital gonorrhea within the United States, 6,735 pretreatment gonococcal isolates were tested for their in vitro resistance to penicillin. By using a regression analysis technique, we examined 99 patient-associated variables which might be associated with penicillin resistance of the isolates. Patients were most likely to have relatively resistant isolates if they were black, had used antimicrobial agents within 2 weeks of treatment for gonorrhea, or were men with symptomatic urethritis.