The effects of insulin and granulocyte-macrophage colony stimulating factor (GM-CSF) on the expression of transferrin receptors in AML-193 myeloid leukemia cell line were investigated. Insulin, alone or in combination with GM-CSF, caused an increase in surface transferrin receptors within 5 min. This increase was inhibited by hyperosmolarity but not by cycloheximide suggesting the involvement of receptor recycling from internal pools. In contrast, receptor increase after 18 h of incubation with insulin and GM-CSF was sensitive to cycloheximide indicating that long term effects of these growth factors are mediated through protein synthesis. These results may have implications on combined GM-CSF + antitransferrin receptor antibody therapy of leukemias.