The etiology of idiopathic portal hypertension (IPH) is not known. To obtain clues to the pathogenesis, an attempt was made to produce a hepatic lesion similar to that in IPH by repeated injections of aggregated killed non-pathogenic E. coli directly into the portal vein. In the treated dogs, histology of the liver showed dense fibrosis in the portal tract and an aberrant vasculature around the portal area after 1 month. Portal pressure was elevated and middle-to-small-sized portal branches were decreased in number as studied by portography. These changes closely mimic those seen in human IPH. The possibility is discussed that chronic entrance of an antigen such as bacteria from the intestine to the portal venous system plays an etiologic role in IPH.