Sisomicin and gentamicin were tested in vitro against 222 clinical isolates of pathogenic bacteria using the ICS agar dilution procedure. The two drugs were comparable in terms of overall activity although statistical analyses of the data revealed significant differences in their activity against several genera. Sisomicin was significantly more active against Pseudomonas aeruginosa (p < 0.001), Proteus mirabilis (p < 0.005), and Escherichia coli (p < 0.01); gentamicin was significantly more active against Klebsiella (p < 0.001). In most instances, 4.0 μg/ml of either drug was inhibitory for 90% or more of the isolates of each genus tested