In the present study we evaluated the possibility that patients with severe combined immunodeficiency (SCID) might be deficient in lymphoid progenitor cells in bone marrow. Bone marrow from six patients with SCID was studied for the presence of cells expressing antigens associated with the earliest known stages of lymphopoiesis--terminal transferase (Tdt), the common acute lymphocytic leukemia antigen (CALLA), and p24. Four of six patients had detectable Tdt+, CALLA+, and p24+ cells, although they were quantitatively reduced compared to results from normal infant marrow. In two of six patients no bone marrow mononuclear cells expressing any of these markers were detected. These two patients were more lymphopenic than the other four SCID patients. The absence or deficiency of Tdt+, CALLA+, and p24+ bone marrow cells in some patients with SCID (two of six in the present study) is consistent with the lymphopenia seen in these patients and suggests that the underlying defects which result in SCID affect the production of immature as well as more differentiated lymphocytes.