Studies were carried out to evaluate the prevalence and risk factors for antibiotic-resistant Neisseria gonorrhoeae infections. Monthly surveillance of gonococcal isolates showed the prevalence of gonococci with high-level, plasmid-mediated tetracycline resistance (TRNG) to be about 15% for three consecutive 6-mo periods. Over the same period, the prevalence of gonococci with chromosomally mediated resistance to penicillin G steadily increased, from 0% to 9% and then to 21%. From April to July 1987, while chromosomally mediated penicillin resistance was rapidly increasing, a more intensive study was conducted. Patients infected with TRNG reported significantly more lifetime sexual partners (P<.05) but otherwise resembled patients infected with antibiotic-sensitive gonococci. Patients infected with chromosomally mediated penicillin-resistant gonococci differed from other patients. In addition to reporting more lifetime partners (P <.05), patients with chromosomally mediated penicillin-resistant gonorrhea were more likely to be older (P <.05) and more often reported past episodes of gonorrhea (P<.05), greater numbers of recent sexual partners (P <.05), new sexual partners (P <.05), prostitute contact (P =.06), and parenteral drug use or sexual partners who were drug users (P =.07). The introduction of antibiotic-resistant N. gonorrhoeae into communities may be attributable to a subset of patients who practice “risky behaviors” and who could be targeted for disease intervention activities. © 1989 by The University of Chicago. All Rights Reserved.