Escherichia coli expressing F4 fimbriae is the major pathogenic bacteria that causes diarrhea in piglets before weaning. The adhesion of E. coli to the brush borders of the epithelial cells of piglets is the precondition leading to diarrhea, which in turn is due to the presence of the F4 receptors determined by an autosomal recessive gene on the brush borders of the epithelial cells. In order to clarify the genetic mechanism of the adhesion, an in vitro adhesion experiment was carried out for three variants of E. coli F4 (ab, ac, and ad) in 366 piglets of three pig breeds [Landrace (LR), Large White (LW), and Songliao Black (SB)]. The results showed that there existed significant differences (P<0.001) in the adhesion percentage among the three breeds. Most SB piglets were nonadhesive for all the three variants, whereas most LR piglets were adhesive. Within each breed except for LR, the proportions of the three F4 variants adhering to the brush borders differed significantly. According to the patterns of the adhesion of the three F4 variants in the three breeds, it is very likely that the three F4 variants F4ab, F4ac, and F4ad have different receptors that are controlled by three different loci.