A possible role of humoral factors in the pathogenesis of vinblastine-induced thrombocytosis was examined. The thrombopoietic activity in serum of experimental animals was tested for its ability to stimulate the incorporation of 75-Se-selonemethionine into platelets of thrombocythaemic mice. The administration of low doses (0.1--0.5 mg/kg body wt.) of vinblastine to rabbits caused a significant increase in serum thrombopoietic activity. Higher doses of vinblastine (1--5 mg/kg body wt.) also increased the serum thrombopoietic activity, but this increase was preceded by a transient drop in the platelet count of peripheral blood. This thrombocytopenia could have been a stimulus for an increase in thrombopoietic activity, through a compensatory feedback mechanism. The vinblastine-induced increase in thrombopoietic activity was abolished by bilateral nephrectomy but not by bilateral ureteral ligation. These data suggest that kidney tissue may be a major source of the serum thrombopoietic factors.