We examined transient and steady-state responses of the pulmonary circulation to hypoxia in isolated pig lungs perfused with autologous blood. Responses were quantified by the pulmonary artery pressure at a flow of 1 l/min (Ppa1) read directly from pressure-flow recordings. Alveolar carbon dioxide tension was constant at 38 Torr and alveolar oxygen pressure (PAO2) was varied between 670 and 0 Torr. When PAO2 was lowered progressively every 10 min, the relation between PAO2 and Ppa1 was sigmoidal, with maximum constriction occurring at a PAO2 of 0 Torr; however, if Ppa1 was allowed to reach a steady state at each level of PAO2, the relation was reproducibly and reversibly biphasic. Ppa1 increased as PAO2 decreased from 670 to 60 Torr, was maximum and stable at PAO2 between 60 and 30 Torr, and decreased as PAO2 was lowered from 30 to 0 Torr. As a result, steady-state Ppa1 at PAO2 greater than or equal to 200 Torr was similar to that at PAO2 = 0 Torr. When PAO2 was changed from 200 Torr to a constant lower level, Ppa1 required 20-30 min to achieve a steady state at PAO2 greater than or equal to 25 Torr and 40-50 min at PAO2 of 10 and 0 Torr. With the latter, the responses consisted of vasoconstriction followed by marked vasodilation. Thus pulmonary vasomotor tone was a complex function of both PAO2 and time. Attempts to explain the pulmonary vascular response to hypoxia must take these complexities into account.