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Common lots of reference MIC (minimum inhibitory concentration) method reagents were used to monitor ofloxacin, a newer fluoroquinolone, and 13 other drugs against 3200 recent clinical isolates in February-April 1992. Five medical centers in the United States and Canada contributed 640 strains per facility as follows: Escherichia coli, Staphylococcus aureus, coagulase-negative staphylococci, Klebsiella spp., and Pseudomonas aeruginosa (100 strains each); Streptococcus pneumoniae (40 strains); and Enterobacter cloacae, Serratia marcescens, Salmonella spp., Haemophilus influenzae, and Moraxella catarrhalis (20 strains each). Quality-control strains were processed concurrently, MICs recorded, and data processed at a common location. Selected ofloxacin-resistant isolates were retested at a reference laboratory to confirm resistances and determine cross-resistant patterns. Results indicate the following (a) fluoroquinolones were superior in usable spectrum of activity to other orally administered drugs (for example, cefaclor, cefixime, ampicillin, amoxicillin-clavulanate, minocycline, oxacillin, and trimethoprim-sulfamethoxazole); (b) ofloxacin and ciprofloxacin were generally equal to gentamicin and cefotaxime against commonly isolated Gram-negative pathogens; (c) fluoroquinolone resistance was rare among enteric bacilli, pneumococci (ciprofloxacin > ofloxacin), H. influenzae, and M. catarrhalis, but more common among oxacillin-resistant staphylococci and P. aeruginosa; (d) cross resistance was generally observed between ofloxacin and ciprofloxacin but was species or genus dependent; and (e) a new fluoroquinolone, levofloxacin, demonstrated promising activity against contemporary pathogens.