Porcine postweaning Escherichia coli enteritis is a cause of significant morbidity and mortality in pigs worldwide, and effective prevention remains an unsolved problem. This study examined the correlation between susceptibility of pigs to experimental infection with an E. coli F18 strain and the porcine intestinal F18 receptor genotypes. Thirty-one pigs classified as either belonging to the susceptible or the resistant genotype were inoculated with cultures of an E. coli O138:F18 isolated from a pig with postweaning diarrhoea. Susceptibility to colonisation and diarrhoea was assessed by clinical observations, faecal shedding of the challenge strain, histopathology and microscopic adhesion tests. Ten of 14 (71.4%) genetically susceptible pigs and one of 17 (5.9%) resistant pigs developed diarrhoea attributable to the challenge strain. There was no difference in susceptibility between homozygotic and heterozygotic susceptible pigs. Faecal shedding of the challenge strain correlated with the genetic receptor profile. Twenty pigs examined immunohistochemically revealed focal to extensive small intestinal mucosal colonisation by E. coli O138:F18 in nine of 10 susceptible and three of 10 resistant pigs. Results of in vitro adhesion assays performed with F18 cells on enterocyte preparations from 24 pigs, showed complete concordance with the F18 genotypes. In conclusion, this study showed a high correlation between the porcine intestinal F18 receptor genotypes and susceptibility to disease. However, pigs of the resistant F18 receptor genotype were not entirely protected against intestinal colonisation by E. coli F18.