Systemic bacterial lipopolysaccharides (LPS) induce inflammatory responses characteristic of sepsis. Instillation of LPS into rat bladder produces a localized inflammatory response similar to that seen in urinary tract infections (UTIs). Four hours after intravesical instillation of LPS, neutrophils infiltrate into the bladder, and mRNA for inducible nitric oxide synthase (iNOS) and the cytokines, interleukin (IL)-6 and IL-10, is detected in rat bladder but not in the kidney. Induction of iNOS protein is inferred because urinary nitrate and cGMP levels are increased 4 hr after LPS intravesical instillation and remain elevated for at least 24 hr. When LPS is injected intraperitoneally, iNOS and IL-6 mRNA are induced both in the bladder and in the kidney. These data are consistent with the effects of intravesical instillation of LPS remaining localized, iNOS activity increases in both particulate and soluble bladder fractions when measured 4 hr after intravesical instillation of LPS. The magnitude of these increases in iNOS activity in the bladder is not as great as when LPS is injected intraperitoneally. Intravesical instillation of LPS induces no increase in lung or kidney NOS activity. The localized inflammatory response produced by intravesical instillation of LPS demonstrates the importance of LPS as a mediator of the host response in UTIs and supports the use of urinary measurements of nitrate and cGMP in humans as indicative of the localized induction of iNOS in UTIs.