Previously, we isolated and characterized an /-A-restricted alloreactive T helper (Tn) 1 component from an allogeneic effect factor (AEF) produced across an H-2 incompatibility using graft-versus-host reaction (GVHR)-act ivated responder T cells and irradiated stimulator spleen cells (1). This AEF component was purported to be a secreted form of a T cell Ia alloantigen receptor. In this report, we extended these studies by the characterization of the TH components of an AEF produced across the same H-2 incompatibility using GVHR-act iva ted responder T cells and irradiated stimulator T cell-depleted spleen cells. The use of such a stimulator cell population reduced the chance that any detectable /-A-restricted AEF TH components were products of stimulator T cells (2). We also introduced some modifications to our method of biochemical fractionation of AEF that enabled us to detect both selfreactive and alloreactive/-A-restricted Tn components. Comparat ive functional and molecular analyses of these two /-A-restricted components suggest that they are structurally distinct responder T cell-derived Ia molecules that recognize/-A-encoded determinants on antigen-presenting cells (APC) of the responder and stimulator haplotypes, respectively. The data are discussed in terms of their relevance to the molecular basis of T cell alloreactivity.