Our previous studies suggested that a defect in the hemopoietic microenvironment of bone marrow occurred in the anemia of chronic inflammatory disease. We examined the in vivo hemopoietic and marrow stromal cell (MSC) response of shielded marrow to 5000 rad leg-irradiation (5000 rad LI), the in vitro growth of BFUE, CFUE, and CFUC in co-culture with MSC, and the in vitro characteristics of MSC. One month after 5000 rad LI, erythroblasts and MSC fell to 18% and 26% respectively. BFUE and CFUE in shielded marrow increased 1.5 to 2 times. Total CFUS and CFUC were normal. In co-culture, small numbers of MSC enhanced BFUE and CFUE, but suppressed CFUC. MSC in colonies were polygonal cells with a plating efficiency of 10 per 10(6) nucleated marrow cells and 1 per 10(6) spleen or nucleated blood cells. MSC were not phagocytic and did not stain with nonspecific esterase. We conclude that in mice with an inflammatory response to 5000 rad LI: 1) Erythroblasts and MSC decreased while erythroid progenitors (BFUE and CFUE) increased in the shielded marrow, 2) MSC stimulated BFUE and CFUE in co-culture, 3) MSC in colonies were adherent, large polygonal cells that may enhance erythroid maturation in the bone marrow.