We have studied the effect of dialyzable transfer factor therapy on three patients with immunodeficiency disease and in one patient who demonstrated no evidence of deficiency of either humoral or cellular immunity. We found evidence for nonspecificity in the effect of transfer factor on mixed lymphocyte culture reactivity. The data suggest that in patients with immunodeficiency disease a maturation of lymphocytes may lead to a generalized increased immune responsiveness. More profoundly, our data show that transfer factor may induce changes in the expression of histocompatibility determinants. We observed changes in the expression of determinants capable of stimulating in the mixed lymphocyte culture reaction as well as an increase in the capacity of lymphocytes to respond.