The proliferation of bone marrow (BM)-derived fibroblasts and granulocyte-macrophage progenitors (GM-CFC) was studied in culture in 23 patients with acute leukemia (AL). The number of GM-CFC colonies was significantly lower in patients with infiltrated BM when compared to those in remission: 17 ± 12 vs. 125 ± 35 colonies per 2 × 105 cells (p < 0.005). The proliferation of fibroblasts derived from leukemic BM was significantly more active in acute nonlymphocytic (ANLL) than in acute lymphoblastic leukemia (ALL): 6.8 ± 3.2×105 vs. 2.8 ± 1.8×105 fibroblasts per flask (p < 0.05). The reduced GM-CFC colony formation correlated significantly (r = 0.84; p < 0.02) with the reduced fibroblast proliferation in patients with ALL but not in those with ANLL. Supernatants from fibroblast monolayers stimulated additionally normal GM-CFC cultured in the presence of a potent conditioned medium as the source of colony stimulating activity. Fibroblast supernatants derived from BM with leukemic infiltrates, stimulated the incorporation of 3H-thymidine by monolayers of normal bone marrow fibroblasts but had no effect on ANLL fibroblasts.