We examined surgical liver specimens from 52 patients with hepatitis C virus-related cirrhosis. All patients underwent orthotopic liver transplantation at Paul Brousse Hospital. They were found to be seropositive for antibodies to hepatitis C virus by second-generation testing (RIBA 2, Ortho Diagnostic Systems Inc, Westwood, MA). We detected multiple granulomas in five (10%) of the cirrhotic livers. These granulomas were composed of epithelioid cells, sometimes associated with multinucleated giant cells, and were surrounded by small lymphocytes and fibrosis. The epithelioid granulomas were located within the cirrhotic nodules. They were not present within the portal tracts or within the fibrosis. These granulomas were diffusely distributed in the liver. None of the patients with diffuse hepatic epithelioid granulomas had evidence of tuberculosis or brucellosis before transplantation or during the follow-up period (range, 3 to 20 months). They had no detectable cause of granulomatous hepatitis. The role of hepatitis C virus as a cause of epithelioid granulomas is discussed.