A positive correlation (r ⩾ +.47, P ⩽ .01) was found between sensitivities of 147 random clinical isolates of Neisseria gonorrhoeae to all possible pairs of the drugs penicillin, tetracycline, erythromycin, chloramphenicol, acridine orange, and ethidium bromide. High-level resistance to streptomycin was also positively correlated with increased resistance to some of these drugs. This suggested that multiply-resistant strains are not exclusively the result of selection of independent mutants for resistance to each drug and that there may be a common mechanism for resistance to some or all of these drugs. This hypothesis was supported by the demonstration that low-level resistance to a large group of drugs (penicillin, tetracycline, erythromycin, chloramphenicol, rifampin, ethidium bromide, and acridine orange) could be lost as well as restored by a single mutational event in vitro.