The efficacy of single-dose therapy with trimethoprim-sulfamethoxazole (TMP-SMZ) and the cost-effectiveness of routine urinalyses and cultures were studied in a prospective randomized trial of 200 women who presented with symptoms of acute lower urinary tract infection. Without the physician's knowledge of the results of urinalysis or culture, the patients were randomly assigned to receive either a single dose or a 10-day multiple-dose course of TMP-SMZ and were followed up for 6 months. Of the 136 patients with positive urine cultures, 68 received single-dose therapy with TMP-SMZ--10 of whom had relapses--and 68 received multiple-dose therapy with TMP-SMZ--only 2 of whom had relapses (P less than 0.02). Fifteen patients in each treatment group experienced reinfection. Side effects of rash and vaginitis were more common in patients who received multiple-dose therapy, but they were mild and well tolerated. Of the 51 patients with urethral syndrome, 48 became asymptomatic after therapy. None of the following tests predicted treatment outcome: pretreatment urinalysis, urine culture or susceptibility testing, antibody-coated bacteria testing, or routine follow-up urinalyses or urine cultures. Empiric therapy with TMP-SMZ in selected women with symptoms of acute uncomplicated urinary tract infection seems practical, safe, and cost-efficient. Considerable savings can be achieved by reserving urinalyses and urine cultures for patients with persistent or recurrent symptoms. Higher cure rates can be expected in patients who receive a standard 10-day course of therapy with TMP-SMZ compared with those who receive single-dose therapy with TMP-SMZ.