The immunology of chronic hypoplastic marrow failure (CHMF, aplastic anemia) was studied in an experimental murine model of the disease induced by busulfan. B lymphocytes of peripheral blood, spleen, and bone marrow were reduced to 30%–40% and T lymphocytes of thymus, spleen, marrow, and blood were decreased to 20%–70% of control values. IgG and IgM antibody titer to sheep red blood cells were reduced to one- third of control levels, and splenic IgG, but not IgM, plaque-forming cells were fewer on day 7 after antigen stimulation. The proliferative responses to phytohemagglutinin or concanavalin A were reduced in cultures of peripheral blood lymphocytes, splenic lymphocytes, and thymocytes, and cutaneous delayed-type hypersensitivity induced by dinitrofluorobenze was not detected in mice with CHMF. The results demonstrate disturbance of a variety of cellular and humoral functions and suggest that the disturbance was due to quantitative and possibly qualitative abnormalities of the cell types subserving these functions. The results suggest that residual cell injury, the lesion underlying experimental CHMF, is not confined to the myeloid stem cell but also involved cells of the lymphoid series.