The bovine fetus is capable of mounting an antibody response when a bacterial antigen (killed Escherichia coli) or viral antigen (live reovirus) is deposited into the amniotic fluid. Time required for the fetus to respond to bacterial antigen given orally (amniotic fluid) is approximately 10 to 14 days and 8 to 10 days for viral antigen. Calves vaccinated prenatally with E. coli from 9 to 102 days before birth and deprived of colostrum survived oral challenge doses of viable E. coli which killed calves not vaccinated prenatally. One mechanism of protection was the local production of antibody in the gastrointestinal mucosa where immunofluorescent techniques showed immunoglobulins IgG, IgM, and anti-E. coli antibody in the duodenum, jejunum, and ileum as well as in the jejunal lymph node. Prenatal vaccination has been used in the field for prevention of colibacillosis. However, the occurrence of some stillbirths and premature births indicates the need for further research before there can be widespread field application of the technique.