Serum alpha-glutathione S-transferase (alpha-GST) has been shown to be a sensitive marker of liver injury. We compared the relationship of both serum alpha-GST and alanine transaminase (ALT) with liver biopsy inflammatory activity in patients who had chronic hepatitis C infection (HCV), and examined the effects of alpha-interferon therapy on serum alpha-GST and ALT concentrations. Of 32 patients with chronic HCV infection studied, 17 received alpha-interferon 4.5 MU three times per week for 3 months and 15 acted as controls. Liver biopsy just prior to treatment was scored for the grade of inflammation (Scheuer histological activity index). Serum alpha-GST and ALT were assayed just prior to biopsy and 3 months later. Neither serum alpha-GST nor ALT levels showed any correlation with baseline inflammation on liver biopsy. alpha-Interferon significantly reduced serum alpha-GST concentration at 3 months (P = 0.01). ALT fell with treatment but not significantly (P = 0.05). Small falls in alpha-GST and ALT were noted in the control group, and when these were considered the significance of the changes in alpha-GST and ALT with treatment was lost (P = 0.35 and P = 0.09, respectively). This study shows that serum alpha-GST is not a useful marker of the degree of liver inflammation in chronic HCV infection, though it may be of more value than ALT in monitoring response to treatment with alpha-interferon.