Stimulation of sensitized lymphocytes by specific antigen in vitro leads to the production of migration inhibition factor (MIF). In the case of the pure soluble protein, or hapten-protein antigens used in the present studies, this MIF production was a property of the T lymphocytes in the cell suspensions. When PPD was used, B cells, as well as T cells, produced MIF. Similarly, PPD could stimulate B cells to mediate the macrophage disappearance reaction, a reaction which is known to be a T cell-dependent in vivo manifestation of cell-mediated immunity. Suspensions of lymphocytes from nonimmune donors could also be stimulated by PPD; in this case, B cells, but not T cells, produced MIF. The factors produced by the two lymphocyte subpopulations appeared to be similar, if not identical, on the basis of physico-chemical criteria. It is suggested that PPD stimulates B cells for MIF production because of its role as a B cell mitogen. The ability of endotoxin lipopolysaccharide, another B cell mitogen, to also induce MIF production by B cells supports this contention. Thus, although activation of lymphocytes for MIF production by specific antigen is a property of T cells, B cells as well as T cells may be so activated by agents which act nonspecifically. This may prove to have implications for in vivo events involved in immunization. In addition, these observations lend further support to the concept that lymphokine production represents a general biologic phenomenon in addition to playing a role in the effector mechanisms for reactions of cell-mediated immunity.