Based on our previous studies on the human normal venous angioarchitecture of the esophagogastric transition segment, we performed a similar analysis in 25 postmortem specimens obtained from subjects with a diagnosis of portal hypertension. The specimens were injected with India ink or barium sulfate and sectioned for histological examination. A ‘weak’ zone (point of lesser resistance) was described as being the most probable site of origin for the development of varicosities in the complex venous system of the esophagogastric junction. Such a system can be considered to be a physiological hemodynamic venous blockade mechanism interposed between the portal system and the systemic veins. The ‘weak’ zone is made up by the scarce submucous veins (shunt veins), by the submucous confluent and final confluent trunks, and by the true perforating veins of the tunica muscularis which compose a venous unity located about 3–5.5 cm above the Z (epithelioglandular) line.