Long-term, low-dose antimicrobial prophylaxis is effective for the prevention of acute uncomplicated urinary tract infection in women. Selected new antimicrobials should be assessed to determine their efficacy for this clinical use. Recommended guidelines for future studies of prophylactic therapy need to address several issues. The study population must be limited to women with recurrent symptomatic uncomplicated urinary tract infection. Antimicrobials studied should be excreted in the urine, with an in vitro spectrum that includes the common uropathogens. An extended half-life may be beneficial. Monitoring during the study should include monthly urine cultures and vaginal, periurethral and rectal colonization studies. The primary outcome measurement is symptomatic urinary tract infection. Secondary outcomes would include asymptomatic bacteriuria, adverse antimicrobial effects, colonization with potential uropathogens, and development of resistance. The comparative regimen should be one of the current standard regimens, trimethoprim/sulphamethoxazole, nitrofurantoin, or trimethoprim.