High-resolution computed tomography (HRCT) was used to evaluate acute morphologic changes in the circulation of anesthetized miniature pigs (a) after volume loading and (b) after induction of hypoxia. Before and after each challenge, serial HRCT scans were obtained at a constant position in the caudal lobes of the lung. Scans were digitized and analyzed to determine the extent of changes in the cross-sectional area of vessels greater than 300 microns in diameter. Parenchymal background attenuation in anterior, middle, and posterior lung regions was used to assess volume changes in vessels less than 300 microns in diameter. Volume loading increased cross-sectional area by 25.2% +/- 4.3 in arteries and by 37.8% +/- 6.1 in veins and caused a gravity-dependent increase in parenchymal attenuation. Hypoxia decreased parenchymal attenuation, which was consistent with constriction of vessels smaller than 300 microns. Larger arteries and veins reacted heterogeneously. Vascular dilation during volume loading was predominantly passive, and hypoxia increased vascular tone throughout the circulation. HRCT represents a new in vivo approach to investigate vascular responses to various stimuli.