To evaluate whether a relationship exists between valproate treatment and transaminase elevations in patients who are positive for hepatitis C virus (HCV). Retrospective medical record review. Veterans affairs medical center. A total of 214 HCV-positive patients; 28 were treated with valproate (study group), 186 were not (control group). Demographic characteristics; valproate treatment histories; plasma concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), albumin, and bilirubin; and exposure to other potentially hepatotoxic drugs, including probable alcohol abuse, were evaluated. Hepatotoxicity was staged by comparing maximum ALT and AST values against upper limits of normal or patients' mean elevated baseline ALT and AST values. Data were analyzed using a logistic regression model. Control patients and those with longer durations of HCV were more likely (p<0.0171 and p<0.0142, respectively) to exhibit higher stages of hepatotoxicity. More valproate-treated patients were exposed to other potential hepatotoxins at the time of peak transaminase elevations (50% vs 39%, p<0.005), whereas more control patients received two or more potential hepatotoxins (13% vs 4%, p<0.00005). Valproate treatment, either alone or in the presence of other potential hepatotoxins, does not appear to be related to increased transaminase elevations in patients with HCV