This paper reviews the effects of pulmonary artery hypertension on gas exchange by exploring three different issues, namely: 1) how does gas exchange behave in diseases characterized by increased vascular tone (primary pulmonary hypertension (PPH), chronic obstructive pulmonary disease (COPD) and interstitial pulmonary fibrosis (IPF)) or decreased vascular tone ("hepatopulmonary syndrome"); 2) how does exercise, as a non-pharmacological tool of increasing pulmonary blood flow, modify gas exchange in these diseases; and 3) how do several drugs that lower (vasodilators) or increase (almitrine) the active component of pulmonary hypertension interact with gas exchange. Available data show that: 1) in PPH a high pulmonary vascular tone enhances gas exchange and when it is lowered, either by oxygen or vasodilators, ventilation perfusion (VA/Q) distributions deteriorate; 2) in COPD a lowered (vasodilators) or augmented (almitrine) active vascular tone is almost invariably paralleled by a deterioration or enhancement of ventilation-perfusion matching, respectively; 3) in IPF an adequate active response of the pulmonary vasculature is essential to maintain gas exchange, both at rest and during exercise; and 4) in patients with liver cirrhosis a low pulmonary vascular tone induces an abnormal VA/Q distribution. In summary, these data show that any situation and/or therapeutic intervention that lowers the active vascular tone deteriorates VA/Q relationships and vice versa. The final effect of pulmonary vascular tone on arterial oxygen tension (PaO2) is less predictable. The reason for this uncertainty is that the actual PaO2 value depends on the interplay of the intra- and extrapulmonary factors that control gas exchange in humans, and not only on the degree of VA/Q mismatching.