We determined the platelet count and MPV in 100 normal subjects, in 147 subjects with thrombocytopenia or thrombocytosis due to other than primary hematologic disorders, and in smaller groups with immune or septic thrombocytopenia or iron deficiency. In these groups, the inverse, nonlinear relation between MPV and platelet count was the same as in a previous study of normal subjects. The same relation between platelet volume and count was found in individual patients as platelet counts rose during recovery from immune or septic thrombocytopenia. The concomitant progressive fall in MPV during recovery from thrombocytopenia, at which times rapidly rising platelets counts were necessarily associated with a population of young platelets, suggests that magnitude of stimulation of thrombopoiesis, not platelet age, is the major determinant of platelet volume. In contrast, as compared to normal persons with similar platelet counts, MPV was increased in subjects with heterozygous thalassemia but decreased in patients receiving chemotherapy for malignancy or renal transplantation. The undefined mechanism of regulation of platelet formation from megakaryocytes, reflected by the inverse relation of platelet size and count, thus seems altered in these disorders. Platelet volume is an easily obtained variable that appears to be useful in the evaluation of abnormal platelet production.