To further characterize the ultrastructure of the human megakaryocytic leukemia cell line, CMK, and its subclone CMK11-5, was observed. Stimulation with platelet agonists, ADP, thrombin, and collagen caused enlargement of vacuoles, projections of the cell surface, appearance of fibrous material in the enlarged vacuoles, and loss of alpha granules. We also found that horseradish peroxidase (HRP) incorporated into the granular structures of the cell could be transported out of the cell. The activation of CMK cells by platelet agonists indicates that human megakaryocytes may be activated in thrombotic states. CMK with particular megakaryocytic properties is a useful cell model for studying megakaryocytic function.