Hepatocyte growth factor plays a key role in liver regeneration but the role of liver in its synthesis in acute liver failure is unclear. We therefore measured hepatic expression of hepatocyte growth factor mRNA in this condition in comparison to H3 histone mRNA, a marker of cellular proliferation. Hepatocyte growth factor mRNA levels were quantified by specific RNase protection assay in nine patients with acute liver failure and found to be similar to those in six normal controls. Hepatocyte proliferation, as assessed by H3 histone mRNA expression, was not detected in normal liver but was present in six of nine patients with acute liver failure (P < 0.05) and was not correlated with expression of hepatocyte growth factor mRNA (rs = -0.28). Liver is unlikely to be the source of the high serum hepatocyte growth factor levels observed in acute liver failure.