BACKGROUND/AIMS: Thrombopoietin is a thrombopoietic factor mainly synthesized in the liver. Its production is regulated by the mass of megakaryocytes and platelets. Impaired production of thrombopoietin may be responsible for thrombocytopenia in chronic liver disease. METHODOLOGY: We studied thrombopoietin serum concentration in 68 patients with chronic liver disease of various degrees (39 with thrombocytopenia), in 5 patients with thrombocytopenia due to hematological disease, and in 27 healthy controls. RESULTS: Thrombopoietin concentration was higher in patients with liver disease than in controls. Patients with hematological disease had much higher thrombopoietin concentration than patients with liver disease. Among patients with liver disease and thrombocytopenia, thrombopoietin concentration was higher in cirrhosis than in chronic hepatitis. A negative correlation was found between platelet counts and spleen size and between thrombopoietin concentration and spleen size. No correlation was found between thrombopoietin concentration and liver disease severity. CONCLUSIONS: Patients with liver disease and thrombocytopenia have serum thrombopoietin concentration higher than normal controls. It seems therefore that the liver, even seriously diseased, maintains the ability to produce thrombopoietin. In the liver patients the number of circulating platelets and the serum levels of thrombopoietin are inversely correlated with the size of the spleen suggesting that thrombopoietin, although normally produced, might be turned over in platelets sequestrated in the spleen.