We characterized 70 consecutive patients with cryptogenic cirrhosis to assess major risks for liver disease. Each patient was reevaluated for past alcohol exposure, scored by the International Autoimmune Hepatitis (IAH) score and assessed for viral hepatitis risks and risks for nonalcoholic steatohepatitis (NASH). The results were compared with 50 consecutive NASH patients, 39 nonalcoholic patients age 50 and over with cirrhosis from hepatitis C, and 33 consecutive patients with cirrhosis caused by primary biliary cirrhosis (PBC). Among the cryptogenic group, 49 (70%) were female, and the mean age was 63 +/- 11 years. Although ascites and variceal bleeding were common, almost one half lacked major signs of complicated portal hypertension. A history of Type 2 diabetes mellitus and/or obesity was present in 51 (73%). Nineteen (27%) patients had a history of blood transfusions antedating the diagnosis of cirrhosis. No clinical or histological features distinguished this group from the other patients, and 14 (74%) of these had a history of obesity and/or diabetes. Nineteen of the remaining nontransfused patients had indeterminant IAH scores but were histologically and biochemically indistinguishable from the others. Twelve of these (63%) also had a history of obesity and/or diabetes. Both diabetes and obesity were significantly more common in the cryptogenic cirrhotic patients compared with the cirrhotic patients with PBC or hepatitis C. In contrast, the prevalence of obesity and diabetes was similar to the NASH patients who were, on average, a decade younger. Although there is some diversity that indicates more than one cause, our findings suggest that NASH plays an under-recognized role in many patients with cryptogenic cirrhosis, most of whom are older, type 2 diabetic and obese females.