Piperacillin/tazobactam (YTR 830; CL-298,741) was tested against fresh and stock clinical isolates of Gram-negative bacilli, as well as against Gram-negative bacilli that had stably derepressed Class I beta-lactamases or that were hyperproductive of non-Class I beta-lactamases. Of 63 clinical isolates of the Enterobacteriaceae with ticarcillin (plus clavulanate) minimum inhibitory concentrations (MICs) of greater than or equal to 128 micrograms/ml, 16 had piperacillin/tazobactam MICs of less than or equal to 16/2 micrograms/ml. Of 48 clinical isolates of Pseudomonas spp. with ticarcillin (plus clavulanate) MICs of greater than or equal to 128 micrograms/ml, 35 had piperacillin/tazobactam MICs of less than or equal to 64/8 micrograms/ml. Tazobactam generally reduced piperacillin MICs by two- to greater than or equal to eightfold against stably derepressed mutants for Class I beta-lactamases.