Norfloxacin is a lipid-soluble weak organic acid bound to plasma proteins to a low extent. Norfloxacin has a pKa1 from 6.2 to 6.4 and a pKa2 from 8.7 to 8.9. Mean concentrations of norfloxacin in prostatic tissue have been reported as 1.7 mg/kg. Recurrent urinary tract infection (UTI) in men is frequently associated with prostatic infection, and chronic prostatitis is both difficult to diagnose and to treat. One hundred and twenty-nine patients were entered into a randomized, open controlled, comparative multiclinic study of the efficacy and safety of norfloxacin vs. co-trimoxazole in male patients with recurrent UTI. Norfloxacin 400 mg and co-trimoxazole 160/800 mg were given twice daily for 4 to 6 weeks. One hundred and nine patients were considered evaluable for efficacy. Norfloxacin effected bacteriologic eradication in 56 of 60 (93%) patients; co-trimoxazole effected eradication in 39 of 49 (67%) patients. This difference in bacteriologic outcome had statistical significance (p less than 0.05). A subset of these patients had prostatic fluid cultures pre- and post-therapy. The eradication rate was 23 of 25 (92%) for norfloxacin and 10 of 15 (67%) for co-trimoxazole. Bacteria isolated were (norfloxacin/co-trimoxazole): E. coli 27/25; K-E-S 14/13; Proteus spp. 7/5; Ps. aeruginosa 2/0; other gram-negative bacilli 4/3; gram-positive cocci 7/3. Four patients, one on norfloxacin and three on co-trimoxazole had drug-related clinical and/or laboratory adverse experiences. None was serious. Norfloxacin appears to be an effective drug for the treatment of recurrent UTI in men.