Blood gases, hemodynamics and ventilation were measured in 7 healthy volunteers at baseline while breathing room air (FIO2 0.21), during hypoxia (FIO2 0.125, 15 min) and after nifedipine 20 mg sublingually at FIO2 0.21 (45 min) and at FIO2 0.125 (15 min). Distributions of ventilation-perfusion ratios (VA/Q) were determined, using the multiple inert gas elimination technique, at baseline, during hypoxia, and again during hypoxia after nifedipine intake. Hypoxia was associated with an average increase in pulmonary vascular resistances by 104%, which was partially inhibited by nifedipine. The inert gas data showed a mild deterioration in the distribution of VA/Q ratios during hypoxia. However, when blood flow and ventilation were constrained to the baseline normoxic values in the distributions recovered during hypoxia ('normalization procedure') a slight improvement in VA/Q matching could be evidenced, which was blunted during hypoxia after nifedipine. This was interpreted as the functional effect of hypoxic pulmonary vasoconstriction (HPV). Using the 'normalized' distributions, we computed the relationship between the decrease in compartmental blood flow that occurred during hypoxia and the corresponding alveolar PO2, and calculated the gain due to HPV feedback using equations of the control theory. The contribution of HPV to the stability of compartmental VA/Q was greatest for alveolar PO2 values around 60 mm Hg, but at best the feedback had only a moderate efficiency.