The adjuvant effect of interleukin 6 (IL-6) entrapped in liposomes was evaluated using a 65 kDa heat shock protein as a model antigen. The secondary humoral immune response either to antigen alone, or incorporated into liposomes, and the effect of IL-6 entrapped in liposomes, on this response were studied in Balb/c mice. The adjuvanticity of these formulations was compared with that of potent adjuvants such as Ribi and dimethyldioctadecylammoniumbromide (DDA). The importance of IL-6 during adjuvant activity was supported by the observation that high serum IL-6 levels were induced in Balb/c mice by all members of a panel of adjuvants tested. Following incorporation into liposomes, IL-6 retained its full biological activity, as shown by its capacity to sustain growth of the IL-6-dependent B9 cell line. At antigen dosages where Ribi and DDA gave minimal or no secondary antibody titres, incorporation of antigen into liposomes resulted in measurable secondary antibody titres. Interestingly, this adjuvant activity was significantly enhanced when liposomes containing IL-6 were co-injected with the liposomal antigen formulation. These results illustrate the potential adjuvant properties of this formulation, which seem especially useful for vaccines containing weak or non-immunogenic antigens.