We have recently described an in vitro clonal assay system for human megakaryocyte-progenitor cells or megakaryocytic colony-forming units (CFU-M). Serum specimens from patients with quantitative platelet disorders were screened for the capacity to alter in vitro megakaryocyte-colony formation. Serum from 11 patients with hypomegakaryocytic thrombocytopenia significantly enhanced the formation of CFU-M-derived colonies (200 to 1840 per cent). Neither serum from eight patients with thrombocytopenia and normal or increased numbers of marrow megakaryocytes nor serum from 11 patients with thrombocytosis altered colony formation. This stimulatory activity has been termed megakaryocytic-colony-stimulating activity (Meg-CSA). The number of megakaryocytic colonies formed was directly proportional to the quantity of stimulatory serum added. Meg-CSA levels appeared to be inversely related to marrow megakaryocyte numbers. The variations in Meg-CSA levels that were detected in different disease states suggest that alterations in the production of this stem-cell regulator have physiologic importance.