The most widely known hypersensitivity reaction of methyldopa, a drug commonly used in the treatment of hypertension, is seroconversion to a positive result of a direct Coombs' test that may lead to a hemolytic anemia. The authors report a case of an infrequently noted, but serious, hypersensitivity reaction to methyldopa, manifesting primarily as acute toxic enterocolitis. A 63-year-old woman was admitted to hospital and underwent aggressive and prolonged investigation of enterocolitis. Withdrawal of methyldopa gave immediate relief of intestinal problems. Rechallenge precipitated a return of symptoms within 14 hours. It is recommended that periodic blood counts and liver function tests be done on patients treated with methyldopa for hypertension. If any abnormalities are noted the drug should be discontinued.