Although several studies have shown that sarcoidosis and tuberculosis are the most common causes of granulomatous hepatitis (GH), these studies were biased because results of unselected liver biopsies and autopsy reports were included. We reviewed the medical records of patients diagnosed with GH at the Mayo Clinic between September 1976 and October 1985 for the current study. Our study group consisted of 45 women and 43 men (mean age, 54.2 years). Overall, 65 patients (74%) were symptomatic; the rest had only liver enzyme abnormalities. The mean duration of symptoms was 19.1 months. Assessment of these patients and a comprehensive workup for infectious agents or other causes revealed idiopathic GH confined to the liver in 50%, sarcoidosis with confirmed extrahepatic disease in 22%, drug-related GH in 6%, tuberculosis in 3%, and other causes in 19%. Our study found a much higher frequency of idiopathic GH than previously published reports, and it represents the largest number of cases of idiopathic liver granulomas reported in a single series.