To investigate whether small B cells can stimulate mixed lymphocyte reactions (MLR), highly purified populations of large vs. small B cell fractions were tested for their capacity to evoke MLR across Mls vs. H-2 barriers. Large B cell fractions stimulated high MLR to Mls and H-2 determinants, irrespective of whether the stimulators were exposed to irradiation or pretreated with mitomycin C. In accord with the findings of others, irradiated small B cell fractions proved to be very poor stimulators of MLR. Significantly, however, mitomycin C-treated small B cell fractions elicited high MLR, particularly to Mls determinants. The finding that small B cell fractions treated with irradiation are poor stimulators of T cells correlates with the known radiosensitivity of B cells. In this respect, the widely held view that small B cells do not have antigen-presenting cell (APC) function rests largely on studies with irradiated B cells. The present finding that T cells respond well to small B cells treated with mitomycin C, however, indicates that small B cell fractions do have APC function. Whether the APC function of small B cells reflects a response to resting B cells per se rather than to cells undergoing activation in vitro, however, remains to be ascertained.