Two sphingosyl galactolipids, galactocerebroside and mixed gangliosides, and two glyceryl galactolipids, mono and digalactosyl diglycerides, were compared for immunological activity in liposomal model membranes. The liposomes were prepared with one of several synthetic lecithins or with beef sphingomyelin. Specific complement-dependent glucose release as was found in all cases, although high titer antiserum was not obtained against monogalactosyl diglyceride. With galactocerebroside, the degree of glucose release was inversely related to the phospholipid fatty acid chain length. The relative efficiencies of these substances in terms of antigenic expression and/or immunogenicity was in the order: ganglioside > digalactosyl diglyceride > galactocerebroside > monogalactosyl diglyceride. Reciprocal serological cross-reactivity was observed between ganglioside and galactocerebroside on the one hand and between mono and digalactosyl diglycerides on the other. Cross-reactivity between these two groups occured in four out of six possible combinations studied. Anti-digalactosyl diglyceride was the only anti-serum with an apparent high degree of specificity and it did not cross-react with either cerebroside or ganglioside. Cross-reactivity was influenced by the phospholipid fatty acid chain length, liposomal antigen concentration and the antibody titer against the immunizing antigen.