Liposomes containing lipid A as an adjuvant and also containing either both (a) cholesterol and gp140 HIV envelope protein or (b) galactosylceramide and a 48 amino acid peptide from the membrane proximal external region of gp41 from HIV, as liposomal antigens were used for immunizing mice. Monoclonal antibodies from each type of immunization were obtained, which recognized either the lipid antigen or the protein (or peptide) antigen separately, or that simultaneously bound to both the lipid and protein (or peptide) antigens, by ELISA. After immunizing with liposomes containing both phosphatidylinositol 4-phosphate (PIP) and peptide antigen, a unique monoclonal antibody was also obtained, which did not bind separately either to the lipid or peptide antigen, or to the liposomes alone, but did bind to the original liposomal antigen containing the peptide but lacking PIP. Our data suggest that immunization with liposomes containing lipid A and also containing both a lipid and protein (or peptide) antigen induces antibodies that recognize broad topographical antigenic liposomal membrane surface patterns. These membrane-specific antibodies have unique binding characteristics.