Background: Granulocyte macrophage colony-stimulating factor (GM-CSF) is an autocrine and a paracrine cytokine which stimulates growth, differentiation and function of myeloid progenitors.Aims: We aimed to Study of GM-CSF mRNA gene expression, its protein and anti GM-CSF antibodies in Acute Myeloid leukemia/Myelodysplastic syndromes AML/MDS patients and their correlation to disease behavior and therapy outcome.Methods: We examined GM-CSF mRNA gene expression by real time PCR (RT-PCR), GM-CSF protein and anti GM-CSF antibodies by ELISA methods in sera of 50 AML/MDS Egyptian cases in comparison with 20 healthy controls and correlate results with disease behavior and response to therapy.Results: There was significant decrease in GM-CSF mRNA gene expression (P value 0.008) and Increase in serum level of GM-CSF Protein (P 0.0001) and anti GM-CSF Ab (P 0.001) in AML/MDS patients in comparison with healthy controls, significant negative correlation between serum level of GM-CSF and initial PB blasts percentage (P value 0.011) and significant negative correlation between serum level of GM-CSF and response to therapy (P value 0.016)Summary / Conclusion: Any alteration in GM-CSF gene expression could have an implication in leukemogenesis and GM-CSF serum level could be used to predict outcome of therapy. Also Anti GM-CSF antibodies play a role in the pathogenesis of AML/MDS and the Usage of anti GM-CSF for disease monitoring and as a marker of disease activity needs larger future studies