Seven Escherichia coli isolates from newborn calves with diarrhea were examined for enteropathogenic properties. One isolate penetrated into HeLa cells, four produced enterotoxin(s) and the remaining two possessed neither of these properties. Penetration of E. coli into HeLa cells was inhibited by antibody in bovine colostrum and in bovine and rabbit immune sera. The effective antibodies appeared to be mostly of the IgM class. The invasion by E. coli isolates was also examined by inoculation of the bacteria into the small intestine of E. coli-immunized and non-immunized guinea pigs. The isolate which penetrated into HeLa cells could penetrate the intestinal mucosa to be disseminated into various organs of non-immunized guinea pigs but not of immunized guinea pigs, whereas no other isolates showed such pathogenicity in vivo. The inhibition of the invasion was observed when non-immunized guinea pigs were inoculated with the bacteria together with colostral or serum antibody. The results show the importance of antibody in the local defense mechanism against E. coli invasion.Colostral immunoglobulins play a crucial role in the survival of the newborn calf (18) and this situation is not comparable with that in other animal species where maternal immunoglobulins are transmitted to the young during fetal life (1). The newborn calf deprived of colostrum will die of colisepticemia associated with diarrhea soon after birth.As reported previously (16), colostrum contains agglutinins directed against various E. coli serotypes and the spectrum of agglutinin titers varies greatly in colostrum samples from different stock farms, probably reflecting the prevalence of particular serotypes of E. coli. The anti-E. coli activity of these colostrum samples was found mainly in the IgM fraction, when assessed by agglutination and opsonization tests. These results suggested that colostral IgM antibody has an important role in protecting the newborn calf from colibacillosis.The enteropathogenicity of E. coli is characterized by distinct properties such as penetration into intestinal epithelial cells (12) and enterotoxigenesis (3,8,13,17) and is related to 0, K and pilus antigens. Some serotypes of 0 and K antigens are isolated more frequently than others from bovine and human cases of diarrhea (5,6,14,15) and certain pilus antigens appear to participate in the expression of the pathogenicity (4, 10).