Spleens from 42 patients with polycythemia vera were studied with immunohistologic technics to assess the degree of hematopoietic cellularity in an attempt to clarify the pathogenesis of the splenomegaly characteristic of this disorder. The 22 spleens obtained in the erythrocytotic phase showed striking congestion with mature erythrocytes but no significant extramedullary hematopoiesis. However, the 20 spleens obtained in the spent phase showed prominent trilinear extramedullary hematopoiesis. Increasing splenomegaly with extramedullary hematopoiesis correlated with the development of increased medullary reticulin and peripheral blood leukoerythroblastosis. Splenic myeloid metaplasia is not a feature of uncomplicated polycythemia vera, and its presence indicates progression to the spent phase, or postpolycythemic myeloid metaplasia. The authors' findings indicate that the presence of hematopoietic precursors in the spleen in the spent phase of polycythemia vera and in agnogenic myeloid metaplasia is a result of their filtration from the peripheral blood.