The in vitro activity of meropenem was compared with those of six other antimicrobials against up to 1,182 clinical isolates of Pseudomonas aeruginosa from 16 North American centers by means of standardized controlled methods. Meropenem was the most active drug. These isolates were less frequently resistant to meropenem (4.2%) than to imipenem (12.5%), ceftazidime (15.6%), piperacillin (21%), ciprofloxacin (16%), tobramycin (26%), or gentamicin (29.8%). Of 147 imipenem-resistant P. aeruginosa isolates, 43.8% were susceptible to meropenem, and 26.9% additional isolates were moderately susceptible to meropenem. Of 49 meropenem-resistant (MIC, greater than or equal to 16 mu g/mL) isolates, 85.7% were also imipenem-resistant, and 24% to 79% were resistant to other antimicrobials. Meropenem MICs were lower than imipenem and ceftazidime MICs for 92 P. aeruginosa isolates from meropenem clinical trials. Carbapenem MICs of greater than or equal to 16 mu g/mL for selected P, aeruginosa isolates from meropenem clinical trials were associated with loss of the similar to 45-kD outer-membrane protein and/or production of type I beta-lactamases. No metallo-beta-lactamases (e.g., ''efficient'' carbapenemases) were detected.