Response to therapy, renal function, and mortality were analyzed in a prospective study of 249 men with bacteriuria followed for up to 10 years. All patients received initial organism-specific antibiotic therapy followed by 2 years of continuous treatment with sulfamethizole, nitrofurantoin, methenamine mandelate, or placebo. Continuous therapy with active drugs delayed recurrence of bacteriuria and reduced acute clinical exacerbations of infection. Patients with pure Escherichia coli bacteriuria, normal intravenous pyelogram, no previous therapy, and a normal prostate had a good prognosis with short-term antibiotic therapy alone. The presence of prostatic or upper urinary tract calculi, pyelonephritic scars, or mixed or enterococcal infections predicted a poor bacteriologic prognosis. In the absence of severe urologic disease or concomitant noninfectious renal disease no patients with persistent bacteriuria developed renal failure. Continuous antibiotic therapy is of value in selected male patients with bacteriuria in reducing recurrence and acute clinical exacerbations of urinary tract infection.