The activities of piperacillin/tazobactam (PTZ) and 10 other beta-lactams were evaluated by a broth microdilution method using the PASCO system in 1078 Escherichia coli and 447 Klebsiella pneumoniae strains isolated from hospitalized patients in a Greek hospital. Overall, 10.5% of the former and 62.6% of the latter strains displayed resistance to PTZ. Most of the PTZ-resistant strains (71.2%) expressed extended spectrum beta-lactamases and were also resistant to broad spectrum cephalosporins and aztreonam. The high rates of PTZ resistance in E. coli and K. pneumoniae and the extensive cross-resistance to other beta-lactams suggest that PTZ should be used with caution in our clinical setting.