Local bone marrow renin-angiotensin system (RAS) is an autocrine-paracrine system affecting normal and neoplastic hematopoiesis. Angiotensin converting enzyme (ACE) converts angiotensinogen-I to its physiologically active peptide angiotensinII, which stimulates proliferation and differentiation of hematopoietic stem cells through angiotensin II type 1 receptors. We investigated the ACE insertion/deletion (I/D) gene polymorphisms in patients with hematological malignancies including acute and chronic leukemia, myelodysplastic syndrome and multiple myeloma. Our results showed that 80.4% of the patients represented ID/II genotype, whereas it was 55.9% of the control group and 3.2 fold increased disease risk in the existence of insertion allele (ID/II). This is the first study demonstrating possible effects of ACE I/D gene polymorphism of the local bone marrow RAS components on leukemic hematopoiesis.