We studied the effects of peripheral blood lymphocytes from 16 untransfused patients with severe aplastic anemia (AA) of diverse etiologies on the growth of granulocyte-macrophage colonies from normal marrows. Normal lymphocytes in our system increased the number of granulocytic colonies by 31 +/- 6% (mean +/- SEM). Lymphocytes from 3 of 16 untransfused AA patients significantly inhibited growth in HLA- matched sibling marrows (-30%, -40%, and -37%; p less than 0.01). Although these results suggest that the majority of cases of AA are not mediated by a coculture-detectable immunologic mechanism, studies using lymphocytes obtained from AA patients before transfusions may detect the subpopulation whose disease is immune-mediated and who may therefore respond to immunosuppressive therapy.