To identify mechanisms whereby antibody to mannose-sensitive pili of Escherichia coli might enhance host defenses, we evaluated the activity of antibody to pili in four antibacterial immune processes. Antiserum to pili and Fab' fragments of IgG antibody to pili inhibited the ability of homologous piliated organisms to adhere to buccal epithelial cells. However, this antiserum did not enhance intravascular clearance, complement-dependent bacteriolysis, or opsonophagocytosis. The addition of antiserum to pili to polymorphonuclear leukocytes and piliated E. coli reduced the rate of killing from 52% to 5%. The addition of complement restored the rate to 52%, but this was much less than the 99% rate achieved with polymorphonuclear leukocytes and either fresh serum or antibody to the whole bacteria. These observations suggest that the principal anti-bacterial property of antibody to mannose-sensitive pili of E. coli is inhibition of bacterial attachment. Whether the anti-opsonic effect of antibody to pili is detrimental to host defense remains to be determined.