Endogenous opioids participate in growth regulation. Liver regeneration relates to growth. Thus, we explored the expression of methionine enkephalin and of the delta opioid receptor 1 immunoreactivities with a polyclonal rabbit antibody in deparaffinized liver of patients with chronic liver disease. Fifteen of a total of fifty-eight samples expressed both opioid receptor and methionine enkephalin immunoreactivities, one sample expressed receptor but not methionine enkephalin immunoreactivity, and two samples expressed methionine enkephalin but not receptor immunoreactivity. Ten of the 45 (22%) samples from patients with chronic hepatitis C, four of the eight (50%) samples from patients with chronic hepatitis B, one of the five (20%) samples from patients with autoimmune hepatitis expressed both met-enkephalin and delta opioid receptor 1 immunoreactivities. The expression of methionine enkephalin and delta opioid receptor 1 immunoreactivities suggests that methionine enkephalin exerts an effect in situ, which may include regulation of liver regeneration. However, another possibility that concerns an effect of methionine enkephalin in the liver arises. As morphine, which acts via opioid receptors, has been reported to increase hepatitis C virus replication in vitro and to interfere with the antiviral effect of interferon, methionine enkephalin, analogous to morphine, may enhance the replication of the hepatitis C virus in the liver of patients with this type of viral hepatitis, and interfere with the therapeutic effect of interferon. These results may explain at least in part, why some patients with chronic hepatitis C infection do not respond to interferon therapy.