We examined bacterial persistence and resistance in the vaginal and fecal flora of 28 women who received a total of 253 months of daily low-dosage prophylaxis with nitrofurantoin macrocystals (100 mg per day) or trimethoprim-sulfamethoxazole (40 and 200 mg respectively). During trimethoprim-sulfamehtoxazole prophylaxis, 8.5% of monthly vaginal and 27% of monthly fecal cultures grew Escherichia coli, as compared to 36 and 96%, respectively for nitrofurantoin macrocrystals. Esch. coli resistant to nitrofurantoin occurred in two of 95 fecal cultures during therapy, and Esch. coli resistant to trimethoprim-sulfamethoxazole in 16 of 182 (8.8%) fecal cultures. In the 12 months before treatment, 92 episodes of recurrent urinary infection occurred, as compared to six during treatment (none occurred on trimethoprim-sulfamethoxazole). These results confirm the value of trimethoprim-sulfamethoxazole prophylaxis for high-risk patient with recurrent urinary infections. Prophylaxis with nitrofurantoin macrocrystals seems adequate for less severe problems of reinfection.