Although there is substantial evidence indicating that platelets are released from megakaryocytes in the capillary bed of the lung, this concept has not been universally accepted because much of the evidence has been indirect. To more definitively substantiate that platelet production takes place in the lungs, megakaryocyte and platelet production was accelerated in mice by phlebotomy or by administration of thrombopoietin, and ultrastructural analysis was performed on lung specimens. Intact megakaryocytes, megakaryocyte fragments with numerous demarcated platelet fields, dissociating intact platelets, and denuded megakaryocyte nuclei were seen in the pulmonary capillaries of mice. In addition, some megakaryocyte nuclei exhibited the morphological counterpart of apoptosis. These observations provide evidence for platelet release in the capillary bed of the lungs during stimulated as well as reactive thrombocytosis without precluding observations that some "proplatelets" form in the sinusoids of the bone marrow before transmigration of intact megakaryocytes into the circulation.