Primary pulmonary hypertension is a rare and generally progressive disease in which mild hypoxemia at rest, with lower PaO2 during exercise, is consistently reported. Severe hypoxemia at rest suggests the occurrence of a right to left intracardiac shunt, most often due to patency of a foramen ovale. Two cases are reported of primary pulmonary hypertension which rapidly developed severe hypoxemia at rest with worsening of pulmonary hypertension, from which interatrial communication was identified. The prognostic and therapeutic implications of this situation are discussed.