In experiments designed to study the co-adjuvant action of interleukin-2, a model antigen (tetanus toroid) was passively entrapped in, or covalently coupled to multilamellar liposomes in the presence or absence of interleukin-2 (IL-2). When present, IL-2 was either co-entrapped with the toroid, entrapped alone in liposomes with toroid coupled to their surface, or coupled to the surface of liposomes with entrapped toroid. The role of spatial localization of IL-2 within the liposomal structure (vis a vis that of the toroid) was studied in terms of its immunoadjuvant action in vivo, Male CD-1 mice were injected intramuscularly twice with a variety of toxoid-containing liposomal preparations in the absence or presence of IL-2 incorporated in the same liposomes as above, In some experiments mice were immunized with liposomal toroid mixed with separately entrapped IL-2. Results show that IL-2 augments significantly secondary immune responses (IgG(1), IgG(a), IgG(2b) subclasses) against the liposomal toroid (up to 15-fold compared with the liposomal toroid alone), regardless of cytokine and antigen mode of accommodation in the liposomal structure but only when both are present in the same vesicles. It is suggested that liposomal IL-2 may prove useful as a co-adjuvant for vaccines which are weak or ineffective.