Preliminary results were obtained from a cooperative study designed to determine the efficacy of continuous therapy with urine-sterilizing agents in the treatment of chronic urinary tract infections. The primary objectives of the study are as follows: [1] to determine the efficacy of continuous therapy with sulfamethizole, nitrofurantoin, methenamine mandelate, and placebo in controlling bacteriuria after specific broad-spectrum antibiotic therapy; and [2] to determine if control of bacteriuria has a favorable effect on renal function. The results of the control of bacteriuria with the various treatment programs are described in detail. Initial broad-spectrum antibiotic therapy was successful in eradicating bacteriuria in 88% of the first 122 patients entered in the study. Methenamine mandelate prevented recurrence of infection in 78% of these cases over a 13-month follow-up period. Nitrofurantoin and sulfamethizole prevented recurrence in one half of the individuals treated compared with only 14% who received placebo therapy. The greater number of courses of antibiotics given for incidental infections and minor variations in the distribution of patients with adverse host factors in the methenamine mandelate group may have contributed to the better response rate with this drug. Unless initial therapy eradicated or severely suppressed bacteriuria, active continuous therapy was ineffective in inducing a bacteriologic response. The patients who received multiple previous courses of therapy for urinary tract infection had a significantly lower response rate to the therapy given in the study. The patients on active continuous therapy required fewer short courses of broad-spectrum antibiotic treatment for clinical exacerbations of urinary tract infection compared with the placebo group during the follow-up period. There was no correlation between symptomatology and bacteriuria, but the urine sediment and stained smear provided a reasonably accurate index in predicting a positive culture. No conclusions can presently be drawn from the renal function studies as to whether or not control of bacteriuria has a favorable effect on renal function.