SUMMARY.In patients with chronic hepatitis C, the therapeutic effect of interferon (IFN) is influenced by the progression of liver disease. In a previous study, we showed that 2′,5′‐oligoadenylate synthetase activity in the liver homogenate was significantly lower in cirrhotic rats than in controls after injection of murine IFN. To determine the reason for this decrease, we injected IFN into rats with thioacetamide‐induced cirrhosis and used microautoradiography with human lymphoblastoid interferon ([125I]LyIFN). Accumulation of [125I]LyIFN in cirrhotic rat livers was approximately half of that in control rats (2880±900vs5770±600mm2,P<0.01). In the cirrhotic rat livers there were few grains on the hepatocytes, but many on collagen fibres. These results suggest that binding of IFN to its hepatocyte receptors is hindered in the presence of cirrhosis. The decreased amount of IFN reaching hepatocytes may contribute to the poor responses to IFN seen in patients with