Wheat germ agglutinin (WGA), added to Mishell-Dutton-type cultures of nude spleen cells challenged with erythrocyte antigens, allows a primary specific plaque-forming cell (PFC) response. WGA, however, does not display direct mitogenicity to either T or B lymphocytes. The activity of WGA in the specific PFC response is macrophage-dependent and parallels a nonspecific PFC response in the same cultures.