Accumulating evidence has shown that marrow failure in some patients with myelodysplastic syndrome is associated with autoimmunity, T-cell mediated myelosuppression and cytokine-induced cytopenias. In this perspective article, Drs. Barrett and Sloand expound on auto-immunity in myelodysplastic syndromes, in particular focusing on what has been learned from study of patients with trisomy 8. See related article on page 496.