Intermittent bladder catheterization (ICP) has become a widely used method of bladder management following spinal cord injury (SCI). However, nosocomial urinary tract infection (UTI) is a frequent complication. Although frequently asymptomatic, UTIs often are polymicrobial and resistant to many antimicrobial agents. Compared with parenteral therapy, treatment with oral agents is usually more practical and cost effective. As part of a larger prospective study to determine whether norfloxacin was effective in the treatment of complicated UTI in SCI patients, we studied a subgroup of 23 recently injured SCI patients on ICP who developed nosocomial UTI with pyuria. Thirty-one strains representing ten bacterial species, including five Pseudomonas aeruginosa, all susceptible to norfloxacin, were isolated from initial urine specimens. Twenty-one patients (91%) had negative mid-treatment cultures. Cultures taken five to seven days after completion of treatment in seven of 23 (30%) remained negative, but persistence of the pretreatment pathogen occurred in three of 23 (13%) and reinfection with one or more new organisms, with or without a persisting pathogen, occurred in 13 of 23 (57%) patients. Clinical cure occurred in three of three subjects with symptomatic UTIs. No side effects were reported. Six of 21 (29%) bacterial strains isolated after treatment were resistant to norfloxacin. Given the limited oral treatment options for UTI and the constant risk of reinfection in this population, norfloxacin appears to be a reasonable choice for many patients. However, as with other antimicrobials, when using norfloxacin in SCI patients, the emergence of resistant bacteria must be carefully monitored.