The ultrastructure of the spleen was studied in four patients with myelofibrosis with myeloid metaplasia (MMM) who underwent splenectomy. The basic structure of the spleen is not altered. Degenerative changes are seen in the white pulp, which appears atrophic. Hemopoietic tissue (erythropoietic and granulopoietic cells, as well as megakaryocytes) is seen in the sinuses, as well as in the cords of the red pulp, but is not seen in the white pulp. Nuclear and cytoplasmic abnormalities are seen in hemopoietic cells. Nuclear changes consist of the nuclear membrane projecting into the cytoplasm and forming nuclear blebs or loops. The nuclear blebs are sometimes connected to the main nuclear body by a stalk containing fibrillar structures. The nuclear loops may be so large as to engulf almost all the cytoplasm. Cytoplasmic changes are degenerative in nature and result in premature destruction followed by phagocytosis. Macrophages are ubiquitous in the red pulp, particularly in association with extracellular reticulum and the basement membranes. They often contain debris of developing hemopoietic cells. These findings support previous studies that indicate that a portion of splenic hemopoiesis in MMM is ineffective.