X-irradiated or normal A mice injected with syngeneic concanavalin A-induced lymphoblasts (syn-Con A blasts) developed inflammatory responses in their footpads 24 to 72 h after the injection of syngeneic lipopolysaccharide-induced lymphoblasts (syn-LPS blasts) into these tissues. This response was designated syngeneic delayed type hypersensitivity (syn-DTH). The Con A blast extracts contain small (apparent MW of 6000-7000) and large (apparent MW of 160,000-175,000) syn-DTH-stimulating antigens, which are found in the total volume (low molecular weight fraction) and the void volume (high molecular weight fraction), respectively, of AcA 44 gel filtrations of this extract. The small and large antigens exhibit different immunological properties. The small antigen of A mouse lymphoblasts induced syn-DTH in X-irradiated (250 rad) mice but not in normal mice, and this immunological activity was elicited with syngeneic but not allogeneic lymphoblasts. The syn-DTH induced with the small antigen was inhibited by Lyt-1+2+, I-Jk+ suppressor T cells or a factor extracted from these cells. In contrast to the small antigen, the large antigen of A mouse lymphoblasts induced syn-DTH in both normal and X-irradiated mice, and this immunological activity was elicited by both syngeneic and allogeneic LPS lymphoblasts. The small and large antigens do not immunologically cross-react, but their immunogenicity is not affected by ultraviolet irradiation, indicating that the immune response against both of them is relatively class II-independent. The possibility that the cellular autoanti-lymphoblast response observed in our studies is in fact a mechanism that down-regulates the lymphoblast activity and thus suppresses the immune response is discussed.