Chronic infection of the prostate with gram-negative bacterial pathogens (mainly coliforms) is a common cause of recurrent urinary tract infections in men. Cure of prostatic infection is difficult because most antimicrobial agents useful against the causative organisms diffuse poorly into prostatic fluid. Pharmacokinetic studies in dogs show that trimethoprim readily reaches therapeutic levels in prostatic fluid, yet clinical studies indicate that only about one-third of men with chronic bacterial prostatitis are cured of infection after prolonged therapy with trimethoprim-sulfamethoxazole. A profound secretory dysfunction of the prostate, characterized by increased alkalinity of solute-poor secretions, often accompanies bacterial prostatitis. Undoubtedly, this secretory dysfunction adversely affects the accumulation of trimethoprim in prostatic fluid and thus accounts for the failure of therapy in some instances. In addition. infected prostatic calculi may account for more such failures than previously realized.