A study was performed in 25 men with spinal cord injuries undergoing intermittent catheterization whose urine had ≥ 105 bacterial colonies/ml to determine efficacy of ciprofloxacin in eradicating susceptible organisms from urine, urethra, and perineum. Cultures were obtained prior to, during, and 5 to 7 days after administration of 500 mg twice daily for 10 days. Organisms in urine were also present in the urethra and/or perineum in 20 cases. Susceptible bacteria disappeared from urine in all subjects; but at follow-up 12 had cultures positive for ciprofloxacin-resistant Gram-positive cocci, including 1 with methicillin-resistant Staphylococcus aureus (MRSA), and 2 with ciprofloxacin-resistant Acinetobacter sp. Treatment significantly reduced Cram-negative bacilli in perinea and urethras, but ciprofloxacin-susceptible organisms were replaced by resistant staphylococci, including MRSA, enterococci, and Acinetobacter sp. We support use of ciprofloxacin for treatment of urinary tract infections in persons with spinal cord injury, but in view of supercolonization with resistant organisms, the drug should be reserved for symptomatic persons not likely to respond to other oral agents.