Cytokines, including interferon (IFN)–g, can be effective immunologic adjuvants but often lack the potency of other, more reactogenic compounds. On the basis of the observation that attachment of IFN-g to antigen could further enhance its adjuvanticity, a chimeric protein involving IFN-g and gp120 of human immunodeficiency virus was produced, using varying lengths of amino acid linkers between the two moieties. All resultant fusion proteins appeared to be dimerized, but full IFN-g biological activity was present only with the longest, 34-aa linker. Immunization with the fusion protein gave rise to enhanced primary antibody responses to gp120, particularly of the IgG2a subclass. In addition, both T cell proliferation and IFN-g production in response to antigen were strongly enhanced by primary immunization with the fusion protein. IFN-g fused to antigen is a more potent adjuvant for Th1-like responses than is IFN-g mixed with antigen.