Piperacillin combined with tazobactam at a fixed concentration (4 mu g/ml) and a ratio (8:1) was tested against 5029 aerobic isolates and 447 fastidious organisms, including anaerobes. Among the Enterobacteriaceae, >95% inhibition was shared only by imipenem (99.1% at less than or equal to 4 mu g/ml), and some newer cephalosporins (95.1%-99.8% at less than or equal to 8 mu g/ml), and piperacillin-tazobactam (95.8% at less than or equal to 16/4 mu g/ml). Piperacillin-tazobactam was the most active agent tested against nonenteric Gram-negative bacilli (93.5% at less than or equal to 8 mu g/ml). Ampicillin-sulbactam was the most active agent against staphylococci (95.0% at less than or equal to 8 mu g/ml), followed by imipenem (91.8%), piperacillin-tazobactam (89.3% at less than or equal to 8/4 mu g/ml), and cefepime (86.2% at less than or equal to 8 mu g/ ml). Against the enterococci, only ampicillin (93.0% at less than or equal to 8 mu g/ml) with or without sulbactam, piperacillin (91.0% at less than or equal to 16 mu g/ml) with or without tazobactam, and imipenem (91.0%) had acceptable activity. Piperacillin-tazobactam and imipenem were the most active drugs tested against all aerobic isolates, inhibiting 93.5% of isolates each. Piperacillin-tazobactam inhibited all fastidious isolates tested, including Haemophilus influenzae (MIC(90), 0.094/4 mu g/ml), Moraxella catarrhalis (MIG(90), 0.064/4 mu g/ml), Neisseira gonorrhoeae (MIC(90), less than or equal to 0.016/4 mu g/ml), and Streptococcus pneumoniae (all MICs, less than or equal to 4/4 mu g/ml). Against the anaerobic isolates, the most broad-spectrum antimicrobial agents tested were imipenem (100.0%), piperacillin-tazobactam (99.5% at less than or equal to 32/4 mu g/ml), metronidazole (98.4% at less than or equal to 8 mu g/ml), and ticarcillin-clavulanic acid (95.1% at less than or equal to 32/2 mu g/ml). These results are nearly identical to a previous study involving the same five medical centers in 1989. Piperacillin-tazobactam appears to remain a highly effective p-lactamase inhibitor combination with a wide empiric spectrum and potency in teaching hospitals.