The efficacy and safety of rufloxacin once daily was compared with that of ofloxacin b.i.d. for therapy of complicated cystitis and upper urinary tract infections. Eighty-three patients were randomly assigned to receive rufloxacin as a loading dose of 400 mg on the first day, followed by 200 mg s.i.d., and 80 received ofloxacin 300 mg b.i.d. Both agents were administered orally for a median duration of eight days. Bacterial elimination rates after treatment were 90% for rufloxacin and 81% for ofloxacin. Half of the treatment failures occurred in patients with infections caused by uropathogens that became either less sensitive or resistant to the quinolones being studied. At a two-week follow-up, recurrences had not occurred in any of the rufloxacin patients and had occurred in 17% of the ofloxacin patients. Minor adverse reactions were reported by 12 and 13 patients, respectively. Rufloxacin once daily is as effective as ofloxacin b.i.d. for the treatment of complicated cystitis and upper urinary tract infections.