Clinical and pathologic features of three patients with chronic intrahepatic cholestasis from birth are described. Each patient exhibited a paucity and hypoplasia of interlobular bile ducts, unusual facies, short stature, a pulmonary ejection systolic murmur, and structural anomalies of vertebrae. This constellation of defects constitutes a distinct syndrome to which the terms arteriohepatic dysplasia and syndromatic hepatic ductular hypoplasia are applied. Clinically, cholestasis was not progressive and, although the SGPT was chronically elevated (122-520 units/liter), features of liver cell failure did not develop. Changes in plasma lipids and lipoproteins and serum bile acids were consistent with chronic cholestasis. Liver biopsies from the three cases revealed pseudoxanthomatous change, increased stainable copper and mild hepatocellular degenerative changes. Electron microscopy of one of the liver biopsies revealed extension of thick bundles of collagen from portal areas into hepatic lobules with obliteration of the space of Mall. With increasing age, portal tracts contained fewer bile ducts. This apparent progression of the lesion was not associated with an inflammatory cell infiltrate, progressive fibrosis, or the development of cirrhosis. © 1981 Digestive Disease Systems, Inc.