Forty women with uncomplicated urinary tract infections were assigned randomly to receive 400 mg. norfloxacin or 160 mg. trimethoprim and 800 mg. sulfamethoxazole twice daily for 10 days. Of the 20 patients receiving norfloxacin none had bacteriuria during or 7 days after therapy and 5 patients were reinfected within 6 weeks of therapy discontinuation. Of the 20 patients receiving trimethoprim-sulfamethoxazole therapy 1 presented with a strain resistant to trimethoprim-sulfamethoxazole and was excluded from the study. The remaining 19 patients were uninfected during and 7 days after therapy, and 6 patients were reinfected 6 weeks after therapy. All documented recurrences were caused by bacteria sensitive to the initial therapeutic agent. Anal and vaginal Enterobacteriaceae maintained their sensitivity to norfloxacin. One patient on trimethoprim-sulfamethoxazole presented with and 2 patients acquired resistant anal and vaginal Enterobacteriaceae. No adverse reactions occurred in either treatment group. Norfloxacin was as effective and safe as trimethoprim-sulfamethoxazole without emergence of resistant bacteria associated with trimethoprim-sulfamethoxazole.