A novel non-covalent method of attaching antibodies to liposomes which exploits the high affinity of streptavidin for biotin, is described. The two-step coupling protocol involves the initial attachment of streptavidin to liposomes containing biotin PE, followed by the coupling of biotinated antibodies to streptavidin-liposomes. The association of streptavidin with liposomes containing biotinated PE is rapid (less than 5 min), resulting in a maximum association of 40 molecules of streptavidin per 100 nm vesicle. In the presence of equimolar cholesterol, the amount of streptavidin bound is twice that observed when biotin PE/egg PC liposomes are used. Irrespective of the mole ratio of biotin to antibody (e.g. for 1-6 biotins per antibody), or the molar ratio of antibody to streptavidin in the second incubation step, equimolar amounts of antibody bind to streptavidin. It is shown that anti-rat-erythrocyte IgG or F(ab')2 complexed to liposomes via the streptavidin linker bind specifically to rat erythrocytes but not to human erythrocytes. This coupling protocol can be readily extended to other biotinated antibodies.