The bacterial flora in the urine samples of 15 nursing home patients with long-term, indwelling catheters were examined monthly for one year. There was a rapidly changing polymicrobial flora averaging 2.0 changes per month in species with colony counts greater than 100,000/mL, and 3.2 changes per month when changes in species, biogram, and quantity of bacteria were considered. The flora changed significantly more frequently, and cultures of Pseudomonas aeruginosa, Providencia stuartii, and Citrobacter diversus were significantly more frequent in those receiving sulfamethoxazole and trimethoprim prophylaxis than in those who did not. There was no difference in incidence of urinary tract infection (UTI) between those patients who received sulfamethoxazole and trimethoprim prophylaxis and those who did not. Ampicillin or gentamicin was effective against 99% of species cultured that are of established UTI pathogenicity. Owing to the rapidity of bacterial flora changes, routine monthly cultures are of little predictive value in patients with indwelling catheters. This study does not support the efficacy of sulfamethoxazole and trimethoprim prophylaxis in such patients.