Nonalcohol-induced fatty liver is widely believed to be a benign condition with little or no risk of disease progression. There have been occasional reports of progression to cirrhosis but none in the absence of preexisting fibrosis on the index biopsy specimen even when co-existing hepatitis was present (steatohepatitis). From our histological database (1978 to 1985), we identified 161 patients with fatty liver seen at our institution and traced the case notes of 156. One hundred five patients were initially excluded as having an alcohol-induced cause, and the remaining 51 either were seen in the clinic (37) or had died, in which cases copies of their death certificates were obtained (14). A further 7 patients were excluded after clinic attendance gave evidence of alcohol excess and another 4 after review of their initial biopsy showed the presence of fibrosis or steatohepatitis. The apparent cause of the steatosis in the 40 included patients with strictly nonalcohol-induced pure fatty liver was obesity in 12, diabetes in 4 (1 obese patient), and cachexia associated with extrahepatic malignancy in 6. Four of the remaining 19 had serological evidence of an autoimmune disorder, but none of these had any clinical or histological features of autoimmune liver disease. Nine patients had evidence of hyperlipidemia, 3 of whom were also obese. At a median follow-up of 11 years (7 to 16), 12 of 26 living patients had abnormal results of liver blood tests and had repeat liver biopsies performed. None had progressed to steatohepatitis or cirrhosis; 1 obese patient had developed mild fibrosis 9.8 years after her index biopsy. The remaining 14 living patients had normal blood tests and liver ultrasound and isotope scans. None of the 14 deceased patients died of a liver-related cause, and none had clinical evidence of liver disease before death. In the absence of preexisting fibrosis or steatohepatitis, fatty liver of nonalcohol-induced origin is an extremely benign condition. (Hepatology 1995; 22:1714-1719).