Effectiveness of cefsulodin in the treatment of urinary tract infections due to Pseudomonas aeruginosa was evaluated by means of a comparative study with 123 enrolled patients. Seventy-four patients whose therapy could be evaluated were randomly assigned to therapy with either cefsulodin at various dosages or an aminoglycoside (gentamicin, tobramycin, or amikacin). In all cases, the treatment course was five to 10 days (mean, 7.4 days), and levels of cefsulodin in the serum of patients administered the lowest dose (250 mg every 6 hr) exceeded the 90% minimal inhibitory concentration (MIC90) of cefsulodin for P. aeruginosa. Cefsulodin therapy cleared P. aeruginosa from 37 of 50 patients, and therapy with an aminoglycoside cleared P. aeruginosa from 16 of 24 patients. The rate of clearance was unrelated to the antibiotic used (cefsulodin, gentamicin, tobramycin, or amikacin) or to whether patients were catheterized, the infectious agent was resistant to carbenicillin or gentamicin or to 4 micrograms of cefsulodin/ml, or the level of cefsulodin in serum regularly exceeded the minimal bactericidal concentration (MBC) for the infecting strain. The mean MIC and MBC for strains isolated from patients who experienced relapse (failure) were not higher than the mean MIC and MBC for strains cleared by cefsulodin.