To determine the role marrow-adherent cells may play in the anemia of chronic diseases, marrow samples were collected from ten patients with the anemia of chronic disease, seven control patients with cancer but without the anemia of chronic disease, and five normal volunteers. Marrow was either cultured directly or first depleted of adherent cells and then cultured. Plasma clots containing 6 X 10(4) nonadherent marrow cells were cocultured with marrow-adherent cells prepared by incubating 6 X 10(4)-6 X 10(2) unfractionated marrow cells in microtiter plates and removing the nonadherent cells. Adherent cell depletion of marrow from patients with anemia of chronic disease significantly increased erythroid colony formation. Coculture of adherent cells from anemic patients with autologous nonadherent marrow cells inhibited erythroid colony-forming unit (CFU-E) proliferation in patients with the anemia of chronic disease. In contrast, adherent cells from control patients did not affect autologous erythroid colony formation, and adherent cells from normal volunteers stimulated autologous erythroid colony formation. Coculture of adherent cells from anemia patients with nonadherent marrow from control patients failed to inhibit allogeneic erythroid colony formation. Media conditioned by adherent cells from patients with the anemia of chronic disease failed to suppress consistently the formation of allogeneic erythroid colonies. These data suggest that marrow-adherent cells normally stimulate erythropoiesis, but suppress erythroid progenitors, in patients with the anemia of chronic disease and may in part be responsible for their anemia.