Severe hepatitis secondary to methyldopa therapy for hypertension was encountered in 6 patients over a 2-year interval. The drug was inadvertently readministered to 1 patient with recurrence of hepatitis within 1 week. One patient died with massive hepatic necrosis. Liver biopsy in the 5 survivors revealed that 4 of them had severe hepatitis with histological patterns indistinguishable from early active stages of chronic aggressive hepatitis. However, all rapidly improved after discontinuation of the drug. The severity of the hepatitis should be considered whenever a person taking the drug develops constitutional symptoms compatible with a hepatitis prodrome, and the drug should be promptly discontinued if chemical evidence of hepatitis is found. A possible drug etiology must be sought in all patients with a histological picture suggesting chronic aggressive hepatitis.