This study is concerned with the pulmonary vasculature in euoxia after preconditioning with 8h of hypoxia. The particular question we ask is whether the pulmonary vasculature will dilate normally with exercise or retain some degree of vasoconstriction, as has previously been reported in studies involving longer exposures to the hypoxia of high altitude. Ten subjects were studied on two separate days. On one day, subjects were exposed to 8h of isocapnic hypoxia (end-tidal P(O)(2) 55Torr) and on the other day to 8h of euoxia as a control. Before and after each exposure, subjects undertook 20min of exercise at an intensity to elevate heart rate (HR) by approximately 30bpm. During this period, Doppler echocardiography was used to assess the maximum pressure gradient during systole across the tricuspid valve (DeltaP(max)) as an index of pulmonary arterial pressure. Following 8-h hypoxia, but not control, DeltaP(max) increased by approximately 2mmHg with the subjects breathing air at rest (ANOVA, P<0.02). Under control conditions, exercise at approximately 30 bpm above resting HR increased DeltaP(max) by 9.9+/-1.3mmHg (mean+/-SE). Following 8-h hypoxia, but not control, this sensitivity of DeltaP(max) to exercise increased by approximately 35% to 13.4+/-2.1mmHg (P<0.05). We conclude that prior conditioning with 8h of hypoxia impairs the ability of the pulmonary vasculature to dilate normally during exercise.