Each month from August 1986 through July 1990, clinical and laboratory data were evaluated for the first 25 urethral isolates of Neisseria gonorrhoeae from men attending a Baltimore sexually transmitted disease (STD) clinic as part of an effort to understand factors that contribute to changes in gonococcal antimicrobial susceptibility. During the 48-month study period, 1193 gonococcal isolates were evaluated; the proportion of penicillinase-producing N. gonorrhoeae (PPNG) isolates steadily increased, the prevalence of tetracycline-resistant N. gonorrhoeae (TRNG) remained relatively stable, and chromosomally mediated penicillin resistance increased steadily during the first 5 6-month intervals, then decreased, only to increase again during the final 2 6-month intervals. Changes in antibiotic treatment regimens for gonorrhea were associated with changes in the prevalence of chromosomally mediated penicillin resistance. In a supplementary study to characterize patterns of antibiotic use among men and women attending the STD clinics, 9% of patients reported antibiotic use in the 2 weeks prior to clinic visit. Antibiotics were taken prior to clinic attendance by 65% of patients reporting antibiotic use, because of concerns regarding possible STD or STD exposure. These patients were significantly less likely to be culture positive for N. gonorrhoeae when compared with patients who did not report antibiotic use. Temporal trends in N. gonorrhoeae antibiotic resistance appear to be influenced by many factors, including treatment regimens and self medication. © 1992 American Sexually Transmitted Diseases Association.