With reports of increasing resistance to antimicrobial agents among Pseudomonas aeruginosa clinical isolates worldwide, the activities of cefepime and eight other broad-spectrum beta-lactams against 6969 isolates collected during 1997-2000 from the four regions of the SENTRY Antimicrobial Surveillance Program. P. aeruginosa isolates were tested by the reference broth microdilution method against nine beta-lactam antimicrobial agents (aztreonam, cefepime, ceftazidime, imipenem, meropenem, piperacillin +/- tazobactam, ticarcillin +/- clavulanate), three aminoglycosides (amikacin, gentamicin, tobramycin), and two fluoroquinolones (ciprofloxacin, levofloxacin). The strains were contributed by more than 100 medical centers. National Committee for Clinical Laboratory Standards criteria were used to identify susceptible and resistant isolates. P. aeruginosa strains from Latin America were generally the most resistant to all classes of antimicrobials, compared with strains from other regions. The beta-lactams exhibited a wide range of potency, with carbapenems most active (meropenem, 80-91% susceptible; imipenem, 76-88% susceptible). Piperacillin/tazobactam was the most active penicillin (77-80% susceptible), and cefepime (67-83% susceptible) had an average 2% (range, 0.7-3.5%) greater susceptibility rate than ceftazidime (66-80% susceptible) across all regions. The rank order of beta-lactam activity according to percent resistant isolates in North American P. aeruginosa strains was: meropenem (4.8% resistant) > cefepime (6.8%) > imipenem (8.6%) > piperacillin/tazobactam (10.3%) > piperacillin (12.9%). Only 2.3% and 6.5% of isolates were resistant to amikacin or tobramycin, respectively, and nearly 16% of P. aeruginosa strains were resistant to ciprofloxacin. Compared with other geographic regions, strains of P. aeruginosa remain most susceptible in North America. In all regions, aminoglycosides in combination with carbapenems, cefepime, or piperacillin/tazobactam would provide more potential antipseudomonal activity than fluoroquinolone combinations for wide-spectrum empiric regimens.