The immunoglobulin heavy chain associated 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 the antigen. To study the immunogenic effect of tuftsin in vivo the peptide was coupled covalently to keyhole limpet hemocyanin (KLH) and bovine serum albumin (BSA) antigens to form stable entities. Tuftsin-antigen conjugates were found to be very potent immunogens as tested by their capacity to increase antigen presentation in culture in primary and secondary responses. Thus, monolayers of macrophages pulsed in vitro with KLH-tuftsin conjugates exerted a stronger immunogenic effect than KLH alone. BSA, which by itself was not immunogenic, when applied to macrophages as tuftsin conjugate evoked a high lymphoproliferative immune response. In vivo, BSA conjugated to tuftsin, when injected in aqueous solutions, augmented significantly antibody production, whereas administration of BSA alone or BSA admixed with tuftsin had no immunogenic effect. Studies conducted to elucidate the mechanisms underlying the activation of the immunogenic function of macrophages by the peptide revealed that treatment of cells with antigen and tuftsin increases secretion of interleukin-1 and expression of cell surface Ia encoded antigens. The effect of tuftsin on increasing the immunogenic capacity of antigens may at least partly be attributed to these effects.