The serum concentrations of soluble HLA-DR antigens (sDR) were monitored in 40 patients with chronic hepatitis C (CHC) who received interferon treatment. The expression of HLA-class II antigens in liver tissues was also studied by immunohistochemistry. The sDR levels in patients with chronic hepatitis C were significantly higher than those in healthy subjects (416+/-236 [mean +/- S.D.] ng/ml vs. 286+/-163 ng/ml) (P<0.05). There was no correlation between the sDR levels and serum alanine aminotransferase levels, suggesting that sDR do not reflect the extent of liver necrosis. Although there was no difference in pretreatment sDR levels between interferon complete responders and non-responders, sDR significantly declined in complete responders, while they did not in non-responders. The hepatic expression of HLA-DR antigens was observed in dendritic cells, lymphocytes and Kupffer cells in portal area, while in Kupffer cells and endothelial cells in central acinus. These expression significantly decreased in complete responders. From these results, sDR, reflecting the hepatic expression of HLA-DR antigens, could be a predictive marker of response to inteferon treatment.