Thirty-two women with recurrent urinary tract infections were treated after eradication of existing infections with a mixture of 40 mg of trimethoprim and 200 mg of sulfamethoxazole thrice weekly at bedtime for six months. Six preadolescents received one half this dose. During 21.3 cumulative patient-years of prophylaxis, one infection due to Streptococcus faecalis and one due to a sulfamthoxazole-and trimethoprim-sensitive Escherichia coli occurred--an infection incidence of 0.1 per patient-year. During prophylaxis, 61 of 72 periurethral cultures and 24 of 51 anal canal cultures failed to yield Enterobacteriaceae. One patient had transient colonization with a trimethoprim-resistant E coli during prophylaxis. Twenty-one patients had recurrent infection within six months of discontinuation of prophylaxis, with a mean time to recurrence of 2.6 months. One infection recurred 26 weeks following prophylaxis with a Proteus mirabilis. Thrice-weekly trimethoprim-sulfamethoxazole therapy was effective for prophylaxis of recurrent urinary tract infections and did not predispose to colonization or infection with trimethoprim-resistant Enterobacteriaceae.