One hundred and sixty-five coded liver biopsy specimens were studied by light microscopy to evaluate the occurrence and diagnostic significance of giant mitochondria, which have been identified as periodic acid-Schiff-negative globular hyaline cytoplasmic inclusions of regular outline, clearly distinguishable from Mallory bodies. In 4 cases, electron microscopy confirmed that these globules were in fact enlarged mitochondria. The incidence of giant mitochondria was significantly higher in patients with high alcohol consumption (72%) than in those with low or no alcohol intake (10%). Their presence was related to the amount of daily ethanol consumption and to the shortness of abstinence before the biopsy. It was independent of other changes in the liver, and was detected with similar frequency in biopsies showing different alcoholic liver diseases. Our study emphasizes that giant mitochondria may be detected by light microscopy in a high proportion of alcoholics, and rarely in nonalcoholic liver diseases. Although less specific, they are much more frequent than Mallory bodies. Consequently they should be considered as a diagnostic hint of recent and heavy alcoholism.