Mice, immunized with liposome-associated bovine serum albumin (LSM-BSA), showed a significantly higher BSA-specific plaque-forming cell (PFC) response than did mice injected with fluid BSA (fBSA). Physical association between the liposome carrier and the protein antigen is imperative for potentiating the PFC response, since the injection of empty liposomes, together with fBSA, was found to be ineffective in inducing an immune response. Liposome-associated protein antigen was found to be a potent stimulator of immunological memory, as demonstrated by the ability of LSM-BSA primed animals to generate a vigorous PFC response upon challenge with the weakly immunogenic fBSA. The injection of congenitally athymic homozygous nude (Nu/Nu) mice with LSM-BSA failed to induce significant antibody formation, whereas the heterozygous (Nu/+) littermates gave a normal PFC response to the same LSM-BSA preparation. Thus, BSA remains a T-cell-dependent antigen, despite its entrapment within liposomes, and T lymphocytes appear to play an obligatory role in providing synergistic interactions for eliciting a BSA-specific PFC response to the LSM-BSA.