The number of spleen Mac-1-positive cells was markedly increased in methylcholanthrene-induced Meth-A fibrosarcoma (Meth-A)-implanted mice. When the sera of Meth-A-implanted mice were added to normal bone marrow cells, granulocyte and macrophage colony stimulating factor (GM-CSF)-dependent growth of bone marrow cells was significantly enhanced. Analysis of the Meth-A-implanted mice sera showed that the levels of serum transferrin were markedly elevated. When the sera of Meth-A-implanted mice were pretreated with anti-mouse transferrin antibody, the enhancement of GM-CSF-dependent cell growth was almost abolished. Cell growth was also stimulated by the addition of transferrin which also caused an increase in the number of Mac-1-positive cells. Analysis of the effect of transferrin on bone marrow cells showed that the response of the cells to GM-CSF was significantly increased by preincubation with transferrin.