In February 1970, 2,321 Capitol Hill employees who were reactors to tuberculin began isoniazid chemoprophylaxis. During the following 9 months, 19 of these employees manifested clinical signs of liver disease. In 9 of the 19, illness began within the first 60 days of isoniazid therapy; the other 10 became ill during the ensuing 6 months. Symptoms included fatigue, anorexia, fever, and gastrointestinal distress; 13 of the 19 were jaundiced, and 2 died. Ten of the patients were women and 9 were men; their mean age was 49.4 years. They could not be linked by person-to-person contacts or by common associations except that each one had taken isoniazid before onset of hepatitis. In a matched comparison group of 2,154 Capitol Hill employees who were unreactive to tuberculin and had not taken isoniazid, hepatitis developed in only one during the same 9-month period. Hepatitis did not occur during this same period in any of 260 tuberculin reactive employees who had declined isoniazid therapy. Although the incidence of liver disease among Capitol Hill employees who were taking isoniazid appears unusually high, the etiologic role of isoniazid remains obscure. Efforts are being made to determine whether the high rates of hepatitis associated with isoniazid in the Capitol Hill prophylaxis program were unique or reflected previously unrecognized morbidity with this drug.