Regulation of pulmonary blood flow was studied during voluntary diving in the aquatic file snake, Acrochordus granulatus. Measurements of pressure and blood flow in pulmonary and systemic vessels indicate that blood flow completely bypasses the lung for significant periods during prolonged and quiescent submergence (greater than 30 minutes). When the lung is ventilated, pulmonary blood flow increases to 36 milliliters per minute per kilogram of body mass (measured in the anterior pulmonary artery), and the cardiac output largely bypasses the systemic circulation. These reciprocating patterns of preferential blood flow reflect inverse relations between flow and vascular resistance, with the result that systemic and pulmonary arterial pressures remain virtually constant throughout repetitive dive cycles. Neuropharmacological studies of freely diving snakes and isolated, perfused lung preparations show that pulmonary blood flow is regulated by an interplay of adrenergic vasodilatation and cholinergic vasoconstriction within the densely innervated lung vasculature. The patterns of blood circulation shown by diving Acrochordus reflect an unusual lability of intracardiac shunts.