The comparative in vitro activity of SM7338 was tested against 670 routine clinical isolates and 130 cefoperazone-resistant isolates of bacteria by agar dilution methods. SM7338 was at least as active as imipenem against gram-negative organisms but was slightly less active against gram-positive organisms. SM7338 was particularly active against members of the family Enterobacteriaceae, with MICs for 90% of strains of less than or equal to 0.125 micrograms/ml for all species tested. Differences in activity between SM7338 and imipenem were particularly striking against Proteus vulgaris, Proteus mirabilis, and Morganella morganii, against which MICs of SM7338 and imipenem for 90% of strains were 0.125 and 4 micrograms/ml, respectively. The presence of unique plasmid-mediated beta-lactamases in Pseudomonas aeruginosa PU21 transconjugants did not affect activity substantially, except in the case of OXA-2 (eightfold-increased MIC) and OXA-3 (fourfold-increased MIC). SM7338 was also active against a laboratory-derived strain of P. aeruginosa which hyperproduced chromosomal beta-lactamase, inhibiting both the wild type and the mutant at a concentration of 1.0 micrograms/ml.