The immunoglobulin heavy chain derived tetrapeptide, tuftsin (Thr-Lys-Pro-Arg), known for its phagocytosis-stimulating activity, was found to augment the antigen-presenting capacity of macrophages in culture, when applied simultaneously with antigen. Injection of antigens or antigens admixed with tuftsin had no immunogenic effect in vivo. On the other hand, antigen-tuftsin covalent conjugates, injected in aqueous solution intramuscularly or intravenously, significantly augmented antibody production. Studying the mechanism underlying these immunogenic effects, we demonstrate that tuftsin, when applied to macrophages together with, or conjugated to, antigens, signals de novo synthesis of mRNA encoding for interleukin-1 (IL-1), and induces secretion of IL-1 from the cells. We suggest that triggering the immunogenic processes by tuftsin conjugates is a consequence of up-regulation of IL-1 synthesis and secretion.