Trimethoprim (TMP) meets all of the theoretical requirements of diffusion into, and actual concentration in, human prostatic fluid. When TMP is combined with the sulfonamide sulfamethoxazole (SMX), potentiation of antibacterial activity is achieved and the development of resistant bacterial strains is less likely to occur. In our initial use of TMP-SMX in the treatment of 13 men with chronic bacterial prostatitis due to gram-negative organisms, patients were given two tablets of TMP-SMX twice daily for only 14 days. The results were that two patients (15%) were cured, nine patients (70%) were improved (sterile prostatic fluid during therapy) but eventually relapsed, and two patients (15%) were unchanged by therapy. In our present study 19 patients (31.6%) were totally cured and 9 of 23 (39.1%) gram-negative organisms were permanently cleared from prostatic fluid; 8 of the 9 patients (42.1%) were improved but eventually relapsed with the same organism; 5 of the 19 patients (26.3%) were considered unchanged by therapy.