To learn whether a single dose of amoxicillin is safe, effective therapy for acute uncomplicated urinary tract infections, 388 symptomatic nonpregnant women were randomly grouped to receive oral amoxicillin, either as a single 3 g dose of 250 mg three times a day for two weeks. Patients had quantitative as well as dip-slide cultures of urine and tests for antibody-coated bacteria in urine. Follow-up urine cultures were obtained one week after completion of treatment. Results of antimicrobial susceptibility and antibody-coated bacterial tests did not alter the randomized therapy. Among 162 patients with bacteriologically confirmed infections, cure rates were 60.6 percent (43 of 71) for single-dose versus 73.6 percent (67 of 91) for two-week treatment (p = 0.07). Although more antibody-coated bacteria-negative patients (89.6 percent; 26 of 29) were cured overall, a substantial proportion of antibody-coated bacteria-positive patients were also cured by both single-dose (59.3 percent; 32 of 54) and 14-day therapy (64.6 percent; 42 of 65). There were fewer adverse effects in the single-dose treatment group. We conclude that a single 3 g dose of amoxicillin, with follow-up urine culture, provides safe and effective management for acute uncomplicated urinary tract infections in nonpregnant women.