Hybridoma antibodies directed against quaternary structural epitopes of the type 1 fimbrial adhesin of Escherichia coli or against D-mannose, the sugar determinant in the complementary host cell receptor, prevented the attachment of mannose-sensitive E. coli to various eucaryotic cells. Passive intraperitoneal administration of the fimbria-specific or D-mannose-specific antibodies protected mice against retrograde colonization with mannose-sensitive E. coli instilled into their urinary bladders. Monoclonal antibodies directed against fimbrial subunits rather than quaternary structural epitopes or against N-acetylgalactosamine rather than D-mannose residues lacked protective activity. These studies provide evidence that bacterial colonization can be blocked or interrupted by antibodies directed against either the adhesin or the complementary host cell receptor of pathogenic microorganisms.