Dendrite cells (DCs) are a new cell type initially identified in mouse lymphoid organs. Recently, DCs have been purified from mouse spleen. This paper demonstrates a functional role of DCs: they are potent stimulators of the primary mixed leukocytes reaction (MLR). As few as 300-1000 DCs doubled the proliferative activity of 5 X 10(6) allogeneic responder spleen cells, while 0.3-1.0 X 10(5) DCs induced a maximal stimulation of 30- to 80-fold. Between these extremes, the log of the MLR response increased linearly with the log of DC numbers. This dose-response assay was then used to compare the potency of purified DCs with that of other heterogeneous lymphoid populations, many of which gave dose-response curves with similar slopes. The potency of purified DCs as MLR stimulators was 100-300 times greater than that of unfractionated spleen cells. When spleen cells were fractionated by simple physical techniques, MLR-stimulating capacity in the subpopulations correlated closely with DC numbers. Removal of splenic B or T lymphocytes, by anti-immunoglobulin or anti-brain serum plus complement, did not reduce MLR-stimulating capacity. Finally, several populations, enriched in mononuclear phagocytes but lacking in DCs, stimulated weakly if at all. We conclude that DCs are a potent stimulating cell and are at least 100 times more effective than other major cell subclasses--i.e., B and T lymphocytes and macrophages.