Intravesical inoculation of patients with Escherichia coli provided an opportunity to examine the interleukin-6 (IL-6) response to a gram-negative bacterial urinary tract infection in humans. All patients secreted IL-6 as a result of infection. Urinary IL-6 was not continuously secreted but appeared as a series of similar peaks during the first 48 h after infection. There was no significant difference in the ability to trigger IL-6 secretion between isogenic adhering or nonadhering strains, but a threshold concentration of 10(5) bacteria per ml of urine was necessary to fully stimulate IL-6 secretion. There was no detectable increase in IL-6 levels in the serum of the colonized individuals, suggesting mainly local IL-6 production. These results demonstrate that IL-6 is a part of the human mucosal response to gram-negative urinary tract infections.