The immunogenicity of different preparations of liposome-associated bovine serum albumin (LSM-BSA) was compared in order to examine the significance of the site of association between a protein antigen and the liposomal carrier. Animals immunized with liposomes containing both entrapped and surface-adsorbed BSA. (LSM-BSA) e + a, were found to give a BSA-specific plaque-forming cell (PFC) response comparable with that elicited by animals immunized with trypsinized (LSM-BSA) e + a which contained mainly entrapped BSA. In contrast, the PFC response elicited by animals immunized with liposomes containing BSA adsorbed on the membrane surface, (LSM-BSA)a, was significantly less than that of the above two groups. Finally, animals injected with trypsinized (LSM-BSA)a only elicited a marginally detectable PFC response. Results of this study demonstrate that liposomes can enhance the antibody response of a protein antigen regardless of whether the antigen is entrapped within the vesicle or absorbed on the outer surface. Entrapped antigen, however, proved to be more immunogenic than that which was surface-adsorbed.