The expression of CD21 antigen, a receptor for the C3d fragment of complement and Epstein-Barr virus (EBV), was investigated in a total of 85 cases of neoplastic lymphoid cells including 39 cases of T-lineage acute lymphoblastic leukemia (ALL)/lymphoblastic lymphoma (LBL), although CD21 antigen is usually regarded as a pan-B antigen. The CD21 antigen was expressed by one of the eight cases of neoplastic lymphoid cells expressing the CD7 antigen as a sole pan-T antigen, by three of the 20 cases of pro- or early thymic stage (CD7+ CD5+ CD2-, CD7+ CD5- CD2+, or CD7+ CD5+ CD2+, and ten of 11 cases of thymic stage (CD3+/- CD4+ CD8+), but not by one case of late thymic stage (CD3+ CD4+ CD8-) T-ALL/LBL cells. The CD21 antigen was not expressed by any of the 11 cases of adult T-cell leukemia (ATL) or two cases of chronic T-lineage leukemia. At most 4% of the normal thymocytes obtained from seven infants or children expressed the CD21 antigen. While only a very limited population of normal thymocytes expresses CD21 antigen, T-ALL/LBL cells at the thymic stage characteristically express CD21 antigen in contrast to pro- or early thymic ALL/LBL or peripheral-stage neoplastic T cells. The estimation of the expression of CD21 antigen is useful for delineating stages of differentiation in T-ALL/LBL. Furthermore, these observation are notable, considering the possibility that the reported EBV-carrying T-cell lymphomas result from the penetration of EBV into EBV-negative neoplastic T cells.