Nosocomial infections by Pseudomonas aeruginosa seen in a general intensive care unit from January 1987 through December 1989 were studied. Use of piperacillin, ticarcillin, cefsulodine, ceftazidime, and imipenem over the same period were recorded. Rate of infection by P. aeruginosa among the 1,844 patients admitted during the study period was 3.2%; 32% of all nosocomial infections during this period were due to P. aeruginosa. The proportion of P. aeruginosa strains exhibiting in vitro susceptibility to ticarcillin rose from 45.5% in 1987 to 59% in 1988 and 86% in 1989. Concomitantly, the proportion of P. aeruginosa strains simultaneously resistant to ticarcillin, piperacillin, cefsulodine and ceftazidime fell from 32% to 18.5% then 0%. A statistically significant correlation was found between the decrease in piperacillin use and the fall in penicillinase-producing ticarcillin-resistant strains of P. aeruginosa. Because piperacillin has undesirable effects on the intestinal flora and promotes the emergence of resistant strains of P. aeruginosa, the authors now use narrow spectrum antimicrobial agents as first line treatment of nocosomial infections.