Pregnant swine were vaccinated with 1 of 2 enteropathogenic strains of Escherichia coli, and their pigs were challenge inoculated with the homologous strain 1.5 hours after the entire litter was born. Seventeen sows were vaccinated orally by feeding viable cultures on 3 consecutive days, 6 sows were given 2 intramuscular (IM) injections of viable cultures at 10- to 14-day intervals, 6 sows were given 2 IM injections fo formolized cultures at 10- to 14-day intervals, and 12 sows were not vaccinated. The pigs from sows which had been orally vaccinated with viable cultures were protected during the 10-day observation period against diarrhea, as well as against death, when the newborn pigs were challenge inoculated with the homologous strain. Most of the pigs from sows which had been vaccinated IM were protected against death, but few neonates were protected against the diarrheal effects of challenge exposure with the homologous strain. Challenge-inoculated pigs suckling nonvaccinated sows had diarrhea and became dehydrated, and many died. Fewer viable E coli were usually recovered from the homogenized intestinal contents or intestinal segments of newborn pigs which did not have diarrhea than from similar specimens of diarrheal pigs. Microscopic examination of segments of the small intestine revealed that large numbers of E coli were closely associated with the ileal mucosa of newborn pigs killed in the acute phase of neonatal enteric colibacillosis caused by either strain, but organisms were not detected in this location in the pigs which remained normal after challenge exposure. It is concluded that swine which have been vaccinated by feeding large numbers of viable E coli late in gestation can provide good protection to their suckling pigs against the effects of challenge inoculation with the homologous enteropathogenic strain.