The growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis is disturbed in cirrhosis, with elevated basal GH and low IGF-I levels relating to liver function and prognosis. In plasma, GH is bound to a high-affinity GH-binding protein (GHBP), which has been found to be slightly reduced in cirrhosis, but with huge variations. GHBP is identical to the extracellular part of the hepatic GH receptor, but other tissues may contribute to the circulating GHBP levels. The aim was therefore to measure circulating and regional concentrations of GHBP in relationship to hepatic function and body composition in patients with cirrhosis (n = 38) and controls with normal liver function (n = 29). Blood samples from the hepatic, renal, and femoral veins and the femoral artery were collected simultaneously during a hemodynamic investigation. Plasma GHBP was directly measured by a specific and sensitive fluoroimmunoassay. Circulating GHBP levels were identical in the patients and controls (mean +/- SD) 1.03 +/- 0.56 nmol/L and 1.02 +/- 0.55 nmol/L, respectively (not significant). We found no significant hepatic, renal, or peripheral arteriovenous extractions or generations of GHBP, and it did not significantly correlate to liver function. In the controls, GHBP correlated significantly with body mass index (BMI) (r =.60, P <.005), whereas this relationship was not found in the patients with cirrhosis. In conclusion, high-affinity GHBP appears to be normal in patients with cirrhosis, with no significant hepatic generation or renal extraction and no association with the severity of the liver disease. Thus, our study supports the hypothesis that tissues other than the liver, despite its abundant GH receptors, may contribute to the circulating GHBP.