We studied the influences of B cells on functional differentiation of T cells using SCID mice grafted with fetal thymus of C.B-17 mice (TG mice). T cells were shown to be reconstituted in TG mice without B cell development. These mice showed normal DTH response to SRBC and OVA. LN cells of these mice produced cytokines including IL-2, IL-4, IL-6 and IFN-gamma according to Con A stimulation. Thus, majority of T cell functions seem to differentiate in the absence of B cells. However, T cells of TG mice failed to proliferate in response to immunizing antigens in vitro, although they responded well to stimulation with Con A. This unresponsiveness of T cells in TG mice to these antigens was restored when antigen-primed B cells were added to the proliferation assay. Such an inability of T cells in antigen-specific proliferation was not seen in SCID mice grafted with C.B-17 fetal liver cells, in which B cells as well as T cells were efficiently reconstituted (FLT mice). T cell proliferation to immunizing antigen was also abrogated in FLT mice when B cells were depleted from lymphoid population. These results indicate that T cells can functionally differentiate and be primed in the absence of B cells, but they require B cells to proliferate in response to foreign antigens.