Urinary tract infections (UTI) remain a common clinical problem; they have especially high morbidity in children and may lead to severe pyelonephritis and bacteremia. Most urinary tract infections have an ascending route with the source of the bacteria in the introital and fecal flora. Following certain types of UTI in humans and experimental animals, there is a local immune response which is characterized primarily by increase urinary immunoglobulins which may exert a locally protective role by coating invading bacteria and thereby blocking receptor sites and interfering with bacteria adherence and initiation of tissue infection. Why certain pathogenic bacteria adhere to and initiate a tissue infection in the lower urinary tract is the subject of this research. If bacterial adherence to urothelial mucosal surfaces can be prevented by immunization, the incidence and morbidity from UTI's can be significantly lessened. The aims of ths research are to 1) define further in animal models of induced UTI the optimal vaginal immunizing regimens for interfering with bacterial adherence to and colonization of urothelial surfaces, 2) study the immunologic response to vaginal immunization in the naimal model and determine adverse or toxic effects of the immunizing procedures, 3) to initiate a limited clinical trial of vaginal immunization against UTI's in adult human subjects. In an animal model, vaginal immunization with formalin-killed bacteria in incomplete Freund's adjuvant has been shown to decrease bacterial adherence as quantitated by an in vivo bladder adherence assay. Vaginal immunization also resulted in faster spontaneous resolution of induced infections. In the proposed work, we plan to further define the best immunizing regimen as to cell wall components used for immunization, optimal adjuvants, cross protection between bacterial species, and the role of bacterial pili in the adherence process. Once the optimal immunizing regimen has been identified in the animal mode, the selected immunizing regimen will be assessed for toxicity in nodes, liver, and spleen. Finally, the optimal immunizing regimen will be applied to a carefully selected group of patient with difficult UTI's in order to assess acceptance by the patients and to help plan an eventual randomized clinical trial.