β-Lactam resistance on the part of the Enterobacteriaceae causes serious therapeutic problems in our institutions due to their production of extended-spectrum β-lactamases (ESβLs). We studied the in vitro activity of β-lactam/β-lactamase inhibitor combinations and third-generation cephalosporins and monobactams against 71 clinically relevant Enterobacteriaceae which produced TEM- and SHV-derivative ESβLs. Of the single drugs and combinations tested, piperacillin/tazobactam proved to be the most effective. Piperacillin/tazobactam was highly active against Proteus mirabilis, with minimum inhibitory concentrations (MICs) ranging from 0.125 to 16 μg/ml; Escherichia coli (MICs from 2 to 16 μg/ml) and Serratia marcescens (MICs from 4 to 8 μg/ml), while its activity against Klebsiella pneumoniae ESβL producers turned out to be closely related to the type and the amount of enzyme produced, the MIC ranging from 1 to 128 μg/ml. The antibacterial activity of piperacillin/tazobactam was stronger than that of ticarcillin/clavulanate, ceftriaxone, cefotaxime, ceftazidime and aztreonam, and the combination shared favorable in vitro activity properties against the ESβL producers with imipenem which, however, should be kept as reserve product.