To investigate the influence of nonlymphocytic leukemic cells on normal erythropoietic burst-forming units (BFU-E), we cocultured leukemic cells at concentrations ranging from 0.5 to 5.0 X 10(5)/ml with 2 X 10(5) blood mononuclear cells or marrow nucleated cells from normal subjects in a BFU-E assay. The inhibitory effect of leukemic cells on burst formation by normal BFU-E was detected only at a high concentration (5 X 10(5)/ml). Leukemic-cell-conditioned medium (LCCM) was prepared by adding 1.25-10 X 10(6)/ml leukemic cells to culture medium. LCCM caused a dose-dependent inhibition of burst formation by normal BFU-E, but the medium prepared from normal cells did not. To examine the influence of fluoxymesterone (FM) on the inhibition of burst formation, we added 10(-10)-10(-7) M FM to the culture medium. Inhibition of burst formation by normal BFU-E was reduced from 73.4% to 58.2%-63.1%. These results suggest that FM stimulates proliferation and differentiation of normal BFU-E that are affected by inhibitory factors produced by leukemic cells.