Lymph nodes and spleens from normal unimmunized mice contain small numbers of CD3+, CD4−, CD8− (double negative, DN) T cells. Of these, approximately one-third express the marker Ly-5(8220) in a form previously seen only on normal B cells and a population of DN T cells found in mice genetically prone to develop autolmmunity. DN T cells proliferate when co-cultured with a syngeneic surface Ig+ lymphoma, CH12. After one cycle of stimulation with CH12 almost all of the responding CD3+ DN cells express Ly-5(B220), suggesting that it is an activation marker for some DN T cells. The CH12 responding population also contains cells with two other phenotypes, Thy-1+, CD4−, CD8−, Ly-5(B220)+, sIgM−, CD3− and Thy-i+, CD4+, CD8−, Ly-5(B220)−, sIgM−, CD3+. The Ly-5(B220)+, CD3− population is no longer found after repeated stimulation. While the relationship between these three populations is unknown, DN I cells can proliferate in the absence of CD4+ or CD8+ cells and therefore their proliferation is not dependent on the presence of other T cells or lymphokines produced by CD4+ or CD8+ T cells. Anti-CD3 Immunoprecipitation of CH12-respondlng cells reveals at least seven different receptor proteins of which five can also be precipitated with an anti-(Cγ1/Cγ2) monoclonal antibody. Thus at least three different TCRγ–δ heterodimers are expressed by CH12-responding T cells. The Thy-1+, CD4−, CD8−, Ly-5(B220)+ cells can provide help to CH12 cells for Ig secretion even in the absence of the nominal antigen for the B lymphoma cells, in summary, these results demonstrate that in normal mice there is a small population of CD4−, CD8−, Ly-5(B220)+ T cells with γ/δ receptors which can provide help for a syngeneic B cell lymphoma.