The expression of L3T4/Lyt-2 on murine T cells has led to the association of these surface markers with recognition of either class II or class I major histo-compatibility complex (MHC) antigens. It has been suggested that these T cell surface antigens interact with nonpolymorphic determinants on MHC antigens. We have examined the role of L3T4 in the recognition of H-2Dd by the T cell hybridoma, 3DT52.5. Mouse L cells transfected with either the H-2Dd gene, or with both the alpha and beta genes of I-Ak and the H-2Dd gene have been used to assess the role of an L3T4/la interaction at varying doses of H-2Dd. A role of L3T4 in activation of 3DT52.5 becomes evident only at limiting doses of antigen. It appears that an L3T4/la interaction can influence T cell function during suboptimal stimulation, implying that the L3T4/la interaction serves to raise the functional affinity of interaction between the T cell and the antigen-bearing cell.