The recently discovered interleukin-15 (IL-15) is known to bind to the receptor of interleukin-2 (IL-2) and to share several of the latter's immunological properties. In the present study, the first to our knowledge on IL-15 behaviour in vivo, we examined the possibility that IL-15 also shares the ability of IL-2 to enhance the immunological adjuvant property of liposomes by acting as a co-adjuvant. The cytokine and a model antigen (tetanus toroid) were either co-entrapped by the dehydration rehydration method into, or covalently co-linked by diazotization to the surface of the same liposomes, or entrapped in different liposome populations. Intramuscular immunization of CD-1 mice with a variety of IL-15 and toroid formulations revealed that IL-15 augments anti-toroid IgG (IgG(1,) IgG(2,) IgG(2b)) responses well above (up to ten-fold) those achieved with liposomal toroid alone (or with a mixture of free IL-15 and toroid) when the cytokine and the antigen are associated with the same vesicles but not when in different vesicle populations that were mixed before injection. Higher responses were observed for all three subclasses studied only with liposomes where IL-15 and antigen were accommodated on their surface. (C) 1997 Elsevier Science B.V.