We studied the efficacy of a fourteen-day course of the fluoroquinolone, norfloxacin, in a group of 69 catheter-free spinal cord injury (SCI) outpatients who experienced a total of seventy-nine urinary tract infection (UTI) episodes. A total of 114 bacterial strains representing twenty species, including sixteen Pseudomonas aeruginosa, all susceptible to norfloxacin, were isolated from initial urine cultures. Mid-treatment cultures in 58/79 (73%) cases were negative. Cultures taken five to seven days after completing treatment in 42 cases (53%) were negative. In the remaining 37 there was persistence of initial or superinfecting pathogen(s), or early reinfection with new organisms. Cultures eight to twelve weeks later in 32 cases with initial eradication showed that 27 (84%) had either relapsed and/or become reinfected. Clinical cure occurred in 4/6 (67%) symptomatic episodes. Side effects occurred in 6 of 73 (8%) patients who received norfloxacin, 4 of whom required withdrawal from the study. Twenty of one hundred twenty-two (16%) bacterial strains isolated during or after treatment were resistant to norfloxacin. Given the limited oral treatment options and the constant risk of reinfection in the SCI population, norfloxacin appears to be a reasonable choice in many patients. However, as with other antimicrobials, when using norfloxacin in SCI patients, the emergence of resistant bacteria must be carefully monitored.