This study was conducted to determine why pigs become highly susceptible to F18+ enterotoxigenic E. coli shortly after weaning. It was suspected that the change in susceptibility was triggered by the change in diet. Either the new diet results in a change in the types of bacteria that inhabit the pig’s intestines and these bacteria affect disease susceptibility, or the high starch content of the weanling diet has a physiological effect on the pigs intestines that result in increased susceptibility to infection and diarrhea. Pigs were reared germ-free from birth for three weeks then given sterile weanling pig feed, a defined population of intestinal bacteria reflective of the intestinal flora, or both. One week later, pigs were challenge-inoculated with F18+ enterotoxigenic E. coli. Unfortunately, none of the pigs developed diarrhea. However, when we measured the number of the pathogenic bacteria in the intestines of pigs receiving either the intestinal bacteria or the sterile weanling pig diet, we observed a significant increase. Further, when we measured the ability of F18+ E. coli to adhere to the brush border surface of intestinal epithelial cells from pigs given either a bacterial flora or the weanling diet, we observed an increased ability for the pathogenic bacteria to adhere. The observations of this study suggest that changes in diet and microbial flora at the time of weaning both contribute to susceptibility of pigs to enterotoxigenic E. coli. We plan further work to more accurately determine what triggers susceptibility to colibacillosis at weaning. These studies may lead to recommendations for the alteration of the weanling diet to reduce susceptibility to colibacillosis without compromising pig performance.