The antibacterial activity of enoxacin was assessed by a standard microdilution susceptibility test method against 6,096 consecutive clinical isolates at four clinical laboratories and compared with that of norfloxacin and cefaclor. Its activity was comparable to that of norfloxacin; both inhibited over 90% of Enterobacteriaceae at 0.5 micrograms/ml. Resistance to enoxacin [minimum inhibitory concentration (MIC) greater than 4 micrograms/ml] was observed in only 18 of 4,076 Enterobacteriaceae (0.5%, 36 of 650 nonfermentative gram-negative bacilli (5.5%), and 6 of 836 staphylococci (0.7%). Relatively poor activity was observed against streptococci. An additional 618 selected clinical isolates were tested with enoxacin and were compared with nine other orally absorbed antimicrobial agents. The greatest activity was observed with enoxacin, norfloxacin, and cotrimoxazole, but some difference were noted with individual species. Results of enoxacin disk diffusion susceptibility testing of 487 isolates were correlated with the MICs, analyzed, and interpretive criteria were determined. With MIC breakpoints of: susceptible = less than or equal to 2.0 micrograms/ml, intermediate = 4.0 micrograms/ml, and resistant = greater than 4.0 micrograms/ml, the corresponding preliminary disk diffusion zone diameter breakpoints for the 10-micrograms enoxacin disk are: susceptible greater than or equal to 18 mm, intermediate 15-17 mm, and resistant less than or equal to 14 mm. Quality control zone diameter limits were determined for three standard QC organisms.