Fab′ fragments of goat anti-rabbit fragment Fab and anti-rabbit fragment Fc were ineffective in the stimulation of transformation of rabbit peripheral lymphocytes. F(ab′)2 fragments had stimulatory activity comparable to that of the intact IgG antibody. Combination of Fab′ fragments of both goat anti-rabbit Fc and antirabbit Fab with the lymphocytes was demonstrated by their capacity to inhibit specifically transformation by the corresponding, intact antibody; in addition, transformation was observed when rabbit lymphocytes, pretreated with univalent fragments of goat anti-rabbit Fc, were subsequently allowed to react with bivalent antibody directed to the univalent fragments. These results indicate that the triggering of transformation by antiglobulin reagents is accomplished through crosslinkage of membrane constituents. Such a mechanism may be relevant to the stimulation of sensitive lymphocytes by antigen and thus may aid in providing a basis for understanding the mechanism of induction and paralysis in the immune response.