Myelophthisic pancytopenia was diagnosed in a 10-year-old pony mare with a history of recurring colic and anemia. Physical findings were unremarkable, with the exception of pale mucous membranes. Hematologic analysis revealed nonregenerative pancytopenia. Testing for equine infectious anemia and antiglobulin (Coombs) yielded negative results. The mare was treated with antibiotics, boldenone undecylenate, and corticosteroids, but a regenerative bone marrow response was not seen. Postmortem examination revealed severe myelofibrosis and multiple sites of extramedullary hematopoiesis. Myelophthisic pancytopenia develops when a space-occupying lesion destroys sufficient bone marrow or disturbs marrow architecture, resulting in decreased production capacity. Pancytopenia in the pony of this report resulted from inadequate production of blood cellular components secondary to replacement of the bone marrow by myelofibrosis. Cause of the myelofibrosis was not identified.