Virulent cells (Ti colony type) and avirulent cells (T4 colony type) of Neisseria gonorrhoeae were grown in a defined liquid medium in the presence of different antimicrobial agents. Bacteria of Ti colony type were found to be more resistant than bacteria of T4 colony type to the inhibitory effects of specific concentrations of ampicillin (0.50 ytg/ml) and penicillin (0.01 ag/ml). Bacteria of T4 colony type, however, were found to be more resistant to the effects of chloramphenicol (0.40 Itg/ml), erythromycin (0.10 ,ug/ml), spectinomycin (10.00 tig/ml), and tetracycline (0.30 ,tg/ml). The differences in susceptibilities of these bacteria to the antibiotics investigated were not due to differences in growth rate or to differences in permeability. The data suggest that virulent gonococci and avirulent gonococci have unique properties that affect their susceptibilities to certain antimicrobial agents.Gonococcal infections in men and women routinely are treated with antimicrobial agents such as penicillin, ampicillin, tetracycline, or spectinomycin (26). The quantities of these antibiotics used in therapy, however, has increased over the years as their effectiveness in treatment of gonorrhea has diminished (13,24,28). Recently, with the emergence of penicillin-resistant (1, 2, 16) and spectinomycin-resistant (1) strains of Neisseria gonorrhoeae, there has been increased concern that treatment of uncomplicated gonococcal infections with these antibiotics eventually may not be sufficient.Although previous studies have shown that antibiotic resistance may result from plasmidmediated resistance genes (2) or from permeability barriers in the cell (20,22) and that multiple antibiotic resistance is derived from clusters of linked genes on bacterial chromosomes (21, 25), there have been few reports comparing susceptibilities of virulent strains and avirulent strains of N. gonorrhoeae to antimicrobial agents. Such data could provide valuable information on metabolic and morphological differences in these strains of gonococci, as well as an insight into the basis of antibiotic resistance in these bacteria.In this study we describe differences in susceptibilities of virulent (Ti colony type) and avirulent (T4 colony type) strains of N. gonorrhoeae to six antimicrobial agents (ampicillin, chloramphenicol, erythromycin, penicillin, spectinomycin, and tetracycline).MATERIALS