To characterize the effects of glucose on the pulmonary vascular response to anoxia and hypoxia, isolated ferret lungs were ventilated with 28% O2 and 5% CO2 and perfused at constant flow (100 ml.kg-1.min-1). Perfusate glucose concentrations were allowed to fall spontaneously to less than 1 mM (low glucose) or were controlled at 5-6 mM (normal glucose) or 12-17 mM (high glucose). At 60, 120, and 180 min of perfusion, the inspired O2 tension (PIO2) was reduced to 0, 10, or 30 Torr for 30 min, and vasomotor responses were quantified by continuous measurement of pulmonary arterial pressure. At PIO2 of 0 Torr, the response consisted of an early phase of transient intense vasoconstriction and a late phase of sustained slight vasoconstriction. High glucose markedly potentiated the magnitude of late-phase vasoconstriction with each successive anoxic exposure. This effect was not reproduced in normal glucose lungs and was not caused by a change in perfusate osmolarity, an action on blood cells, or an altered ability of pulmonary vascular smooth muscle to contract. At PIO2 of 10 Torr, high glucose not only potentiated late-phase vasoconstriction but also slowed the onset of early-phase vasoconstriction. At PIO2 of 30 Torr, high glucose had no effect on vasomotor responses, which were characterized by a slowly developing sustained vasoconstriction. Our results suggest that the vascular response of isolated ferret lungs to severe hypoxia consisted of separate early and late phases of vasoconstriction. This biphasic response may have resulted from two distinct vasoconstrictor mechanisms or from modulation of a single vasoconstrictor mechanism by a secondary vasodilator influence.(ABSTRACT TRUNCATED AT 250 WORDS)