Complications or urinary tract infection may lead to renal failure in persons with neurogenic bladders secondary to spinal cord injury (SCI). Safe, broad-spectrum, oral antibiotics are needed for use in this population. This study evaluates the susceptibility of 980 gram-negative urine isolates, including 68 from SCI patients, to norfloxacin and eight other drugs. Ninety-four percent of isolates from SCI patients and 98% from non-SCI patients were susceptible to norfloxacin. The percentage of strains susceptible to norfloxacin was comparable to that of aminoglycosides and ceftazidime, and was greater than that of mezlocillin, tetracycline, nitrofurantoin, and trimethoprim/sulfamethoxazole. Norfloxacin was the only oral drug showing significant activity against Pseudomonas aeruginosa and was as effective as the injectable drugs. Bactericidal levels of norfloxacin are easily achievable in urine and the drug is generally well tolerated. Norfloxacin may prove to be useful for management or prevention of urinary tract infection in persons with neurogenic bladder dysfunction. Clinical therapeutic and prophylactic trials in this population are indicated.