Although the systemic and local immune response to the O antigen of Escherichia coli has been well characterized, little information is available on the immune response to K anigen. Experimental hematogenous pyelonephritis was produced with Escherichia coli 06 K13 H1 and the serum and local (intrarenal) antibody response to O and K antigens was determined with the enzyme-linked immunosorbent assay. Both local and serum antibody responses to the K antigen were significantly less than that to the O antigen. The K antigen induced low titer IgM and IgG antibody responses in fewer than one-half of the animals and did not induce a local IgA response in any animal. In contrast, the O antigen induced local antibody responses in each of the immunoglobulin classes in all animals from day 9 of infection. Similarly, the serum IgM and IgG antibody titers to the K antigen were significantly less than those evoked in response to the O component of the Escherichia coli. No serum IgA anti-K antibodies were detected. These observations helf clarify the roles of these two antigens in pyelonephritis. Although the K antigen of Escherichia coli functions as a virulence factor in upper urinary tract infections, this antigen does not elicit a significant immune response, whereas the O antigen does induce a significant antibody response which could be of protective or diagnostic benefit.