Animals were depleted of complement using cobra venom factor and the influence of complement depletion on the course of renal infection was studied. Complement depletion markedly increased the susceptibility of renal tissue to a challenge with an E. coli strain sensitive to the bactericidal activity of normal serum, but did not influence the outcome of a challenge with a serum-resistant strain of E. coli. These observations are consistent with the hypothesis that complement-mediated host immune mechanisms do play a role in the biology of renal infection and are an important component of the host's immune response in pyelonephritis.