Piperacillin, a new broad spectrum semisynthetic penicillin derivative, was administered to 22 patients with 25 Pseudomonas aeruginosa infections. All initially responded favorably, although five complicated urinary tract infections and two infections involving prostheses relapsed. In 15 cases, microbiologic eradication of the Pseudomonas was achieved. Failure to achieve a clinical cure was correlated in all cases with the inability to eradicate the organism, which was the result of development of in vitro resistance to piperacillin during therapy (four cases) and of underlying disease impairing host responses. Adverse reactions to piperacillin included leukopenia (eight cases) and nephrotoxicity (two cases).