BACKGROUND--This study was undertaken to determine whether therapy for acute uncomplicated urinary tract infection in women with single-dose therapy with norfloxacin was superior to 3 days of norfloxacin therapy in efficacy or adverse effects. METHODS--The study was a multicenter, prospective, randomized, double-blind trial. Women with acute, uncomplicated urinary tract infection were randomized to receive norfloxacin, 800 mg as a single dose or 400 mg twice daily for 3 days. Clinical and laboratory evaluations were obtained before therapy and at days 3 and 7 and 4 to 6 weeks after initiation of therapy. RESULTS--The 83 subjects for whom data could be evaluated who received 3-day therapy had significantly improved outcome compared with the 73 subjects for whom data could be evaluated who received single-dose therapy at 3 days and 7 days after initiation of therapy. At 4 to 6 weeks, 88% of subjects who received 3 days of therapy remained cured, compared with 78% who received single-dose therapy. Three-day and single-dose therapy were equivalent for Escherichia coli infection, but single-dose therapy was significantly less effective for other organisms, primarily because of failure of treatment of Staphylococcus saprophyticus infection. Women older than 40 years were significantly less likely to be cured with either treatment regimen and with single-dose therapy. Adverse effects were similar for both treatment regimens. CONCLUSIONS -Three days of norfloxacin therapy is more effective than single-dose therapy for women with acute, uncomplicated urinary tract infection. The two regimens are equally effective for E coli infection, but single-dose therapy is ineffective for S saprophyticus.