OBJECTIVE: Valproic acid is frequently not recommended for patients with hepatic dysfunction. The authors evaluated the association between hepatitis C and alanine aminotransferase (ALT) values during valproic acid treatment. METHOD: ALT changes in 564 individuals beginning valproic acid treatment were examined. Changes among those with positive hepatitis C status were compared with changes among patients with positive hepatitis C status who were taking other psychotropic agents. RESULTS: ALT elevations with valproic acid were significantly greater among patients with positive hepatitis C status than those with negative or unknown status. Among patients with positive hepatitis C status, ALT increases did not differ significantly between valproic acid and other medications. CONCLUSIONS: Use of valproic acid may be possible for some patients with hepatitis C. ALT increases in seropositive patients may be partially related to chronic hepatitis infection. However, ALT levels should be closely monitored in all hepatitis C patients taking valproic acid.