The role of T cells in the generation of specific antibodies to antigens under Ir gene control was investigated in strain 2 guinea pigs. The specificity of anti-α,Dnp-Lys9 antibody was studied in guinea pigs with intact immune responses and in strain 2 guinea pigs deprived of T cells by adult thymectomy, lethal irradiation, and reconstitution with syngeneic bone marrow cells. Conventional strain 2 guinea pigs developed both T cell responses and highly specific anti-α,Dnp-Lys9 antibody. In contrast, strain 2 “B” guinea pigs failed to develop delayed hypersensitivity and in vitro T cell responses. Nevertheless, these “B” guinea pigs could produce anti-Dnp antibody of restricted heterogeneity and in quantities comparable to those produced by the conventional strain 2 guinea pigs. It was shown that anti-α,Dnp-Lys9 antibody produced in strain 2 “B” guinea pigs lacking specific T cell responses could not distinguish α,Dnp-Lys9 from dinitrophenol. Similar antibodies are produced in strain 13 guinea pigs that are poly-L-lysine, Ir gene negative. Reconstitution of strain 2 “B” guinea pigs with normal T cells enabled them to develop both cell-mediated immune responses and antibody of highly discriminatory power. These findings support the notion that in the absence of specific T cells, comparably specific B cell antibody responses cannot be generated, and perhaps more importantly, that specific T cells are required to facilitate the amplification of unique B cell clones.