The in vitro activities of piperacillin-tazobactam, 11 other beta-lactam antibiotics, and ciprofloxacin were evaluated in a large multicenter study. A total of 42,208 organisms, collected from 79 listed medical centers and large community hospitals, were tested using the National Committee for Clinical Laboratory Standards broth microdilution procedure. Imipenem (94.7% inhibition), ciprofloxacin (93.8%), and ceftazidime (90.8%) were the most active antibiotics against 31,426 Gram-negative bacilli. Piperacillin-tazobactam (88.8%) and ticarcillin-clavulanate (86.4%) were the most active combination antibiotics against these organisms. Ampicillin-sulbactam (97.8%), piperacillin-tazobactam (96.4%), and imipenem (96.9%) were the most active antibiotics against 10,782 Gram-positive cocci. Overall, the most active antibiotics against all organisms tested were imipenem (95.2%), ciprofloxacin (91.0%), and piperacillin-tazobactam (90.8%).