ABSTRACT— In healthy human livers, L pyruvate kinase (L PK) was detected by immunofluorescence and double labelling in hepatocytes and M PK was detected in bile duct epithelial cells. Numerous associations between isoenzyme type and hepatological lesion were observed. In 10 cases of ethanolic cirrhosis, L and M PK were simultaneously observed in the hepatocytes of regenerative nodules, as they were in biliary neoductules; fibrotic regions were L and M PK negative and the hepatocytes in the anastomosing plate system were almost exclusively L PK positive, as in normal subjects. In 12 hepatocarcinomas, cancer cells had a double L and M specificity with variations in the intensity of the M isoenzyme, while the stroma reaction was L and M negative. In five hepatoblastomas, the simultaneous presence of L and M PK was also observed, but the consistently marked intensity of M PK argues in favour of the embryonic nature of this type of cancer. The results suggest that mature, highly differentiated cells exclusively and specifically synthesize one isoenzyme. A double specificity in pathology reflects the dysfunctional state of the hepatic and biliary epithelial cells or a dedifferentiated state which may terminate with the appearance of a cancer.