PLAY an integral role in maintaining adequate hemostasis. However, the process by which platelets are produced is not well understood. Rodent and human models have been used with varying success in order to unravel the complexities of this biological process.’3 Recently, several comprehensive reviews of this subject have been published summarizing data relating to various aspects of megakaryocytopoiesis.’5 It is the intent of this report to limit the discussion to a critical analysis of the most recent progress that has been made in this field. During the past decade, advances in protein purification and gene cloning have been applied to the isolation and characterization of hematopoietic growth factors. 6’7 In addi-tion, sophisticated means of identifying and isolating rare cell populations have been applied to the study of hemato-poiesis. 8” The adoption of such methodologies has led to many new insights into the means by which cytokines control blood cell production and the determination of the identity of hematopoietic progenitor and stem celIs.” Such informa-tion has had important clinical applications and resulted in the construction of a growing number of useful therapeutic strategies for the treatment of hematopoietic disorders.’2 Recently, these new tools have been applied to the study of megaka ryocytopoiesis, resulting in important advances. A great deal of information concerning mammalian megakaryocytopoiesis has been gained by studying several animal systems, including rodents and man.’3 Megakaryocytopoie-sis in these two different animal systems differs partly because of the important contribution of the spleen to blood cell production in rodents but not in humans. 3 Therefore, many of the observations made in rodents are not totally applicable to the human system, but in the overwhelming number of situations, lessons learned by studying rodents have proven to be true in man.’3 An attempt will be made here to synthesize the information gained by studies of megakaryocytopoiesis in these various animal systems in order to develop unifying concepts that might be generally applicable to mammalian megakaryocytopoiesis.