 Main theoretical concern with the use of pulmonary arterial vasodilator therapy has been worsening of ventilation perfusion matching due to release of hypoxic vasoconstriction. Such a phenomenon is well recognized during prostacyclin infusionGhofrani et al. 895-900;Walmrath et al. 1084-92. Inhaled route seems to circumvent this side effect by preferentially delivering the drug to the alveoli with high VQ ratios and augmenting blood flow to these regions Ghofrani et al. 895-900;Walmrath et al. 1084-92. In the only study to address possible effect of systemically administered sildenafil on gas exchange, Ghofrani et al observed improvement in VQ matching in eight patients using the multiple inert gas elimination technique MIGET. The authors postulated an enhancement of local defense mechanisms against hypoxia i.e. increased nitric oxide availability to hypoxic alveoli despite oral route of administrationGhofrani et al. 895-900. In a recent study of 14 normal subjects, oral sildenafil did not effect DLCO measurements at rest, after exercise and under hypoxic conditionsSnyder et al. 421-30. 