Riluzole is a new drug representing the first active treatment for amyotrophic lateral sclerosis. We report the cases of two patients who developed acute hepatitis after taking riluzole at the recommended dose (100 mg daily) for 7 and 4 weeks, respectively. In both cases, liver histology showed hepatocellular damage with inflammatory infiltration and microvesicular steatosis without fibrosis. Liver enzymes returned to normal 4 and 8 weeks, respectively, after riluzole withdrawal. In one case, the readministration of riluzole was followed by the relapse of hepatitis. These two observations strongly suggest that riluzole can induce acute hepatitis with associated hepatocellular damage and microvesicular steatosis. They also suggest that liver enzymes should be monitored during treatment with riluzole.