The effects of milk gangliosides and their derivatives on the adhesion of enterotoxigenic and enteropathogenic Escherichia coli to Caco-2 cells, a human intestinal carcinoma cell line, were investigated. Human milk gangliosides inhibited the adhesion of enterotoxigenic E. coli to Caco-2 cells in the same proportion, regardless of the lactational stage, but bovine milk gangliosides were less effective. The most effective inhibitor was monosialoganglioside 1 (GM1); the adhesion rate of enterotoxigenic E. coli in the presence of GM1 was less than 20% of the positive control. The adhesion of E. coli was also depressed to 31.4% by monosialoganglioside 3 (GM3). However, the inhibitory effect of disialoganglioside 3 (GD3) was less than that of GM3. GD3 lactone, ceramide lactoside, and N-acetylneuraminic acid did not inhibit E. coli adhesion to Caco-2 cells. GM3 also inhibited the adhesion of enteropathogenic E. coli to Caco-2 cells. Thus, these results suggest that GM3 possibly behaves as a physiological component in the intestinal tract of infants to protect them against enteric infections.