Several lines of evidence point to abnormalities of the phenotype, cytokine responses, and function of cells of the myeiold lineage in non-obese diabetic (NOD) mice. In this study we have characterized the phenotype and myeloid progenitor function of NOD bone marrow. Two hematopoletic differentiation antigens, Ly-6C and AA4.1, are expressed abnormally on NOD bone marrow cells. While multillneage erythromyeloid progenitor cells (day 12 CFU-S) are normal in number in NOD mice, more differentiated myeloid progenitors are deficient in their in vitro responses to IL-3, granulocyte/macrophage colony-stimulating factor (GM-CSF), and IL-5. Since the diabetes-predisposing ldd-5 gene of NOD mice maps close to the IL-1 receptor, we tested NOD bone marrow cells for a defect in synergy between IL-1 and IL-3; no defect was found. The defects in myelopoiesis described here may predispose the NOD mouse to autoimmunlty by impairing macrophage maturation.