This report presents the pooled results from two randomized trials of lomefloxacin and cefotaxime used as prophylaxis in patients undergoing transurethral surgical procedures. A total of 499 patients were enrolled at seven centers in the United States. Patients received either 400 mg of lomefloxacin orally 2-6 hours prior to surgery, or 1 g of cefotaxime intravenously or intramuscularly 30-90 minutes preoperatively. Patients undergoing simple cystoscopy or retrograde pyelograms were not eligible for inclusion. Urine cultures were obtained prior to surgery, 24 hours post-surgery, prior to catheter removal, and 3-5 days post operatively. Treatment failure was defined as isolation of greater than or equal to 10(5) colony-forming units (CFU)/mL of pathogenic bacteria from any post-surgical urine culture. Lomefloxacin was successful in preventing post operative infections in 204 of 207 evaluable patients (98.6%); there were three prophylactic failures. Cefotaxime was successful in 196 of 206 (95.1%) evaluable patients; 10 were prophylactic failures. Lomefloxacin concentrations were measured simultaneously in serum and in samples of prostate tissue from 29 patients undergoing transurethral resection of the prostate. Lomefloxacin prostate concentrations were 1.0-22.3 micrograms/g, with a mean of 5.0 micrograms/g. The average tissue:plasma ratio was 2.0. The safety profile of the two study drugs was excellent, and both were well tolerated. Adverse events were reported by 12.7% of the patients treated with lomefloxacin and 13.8% of those treated with cefotaxime. The majority of events were mild and required no treatment.