The efficacy and safety of piperacillin were compared with those of cefamandole in 72 patients (mean age: 63 years) with complicated urinary tract infections. Efficacy was evaluable in 25/34 piperacillin-treated patients (12 Gm/day) and in 23/38 cefamandole-treated patients (6 Gm/day). Clinical cure or improvement was noted in all patients who were given piperacillin and in 96 per cent (22/23) of those who received cefamandole. Seventy-one per cent (41/58) of the organisms cultured pretherapy were gram-negative aerobic bacteria. Escherichia coli was the most frequently isolated organism (15/58, or 26%), followed by Pseudomonas species (8/58, or 14%), and Proteus species (8/58, or 14%). Adverse clinical experiences were few, and none was directly attributed to therapy with either antibiotic. The changes noted in the results of laboratory tests were considered to be unrelated to the antibiotics administered. Thus, both piperacillin and cefamandole were safe and effective in the treatment of patients with complicated urinary tract infections.