Cardiovascular structure and function were studied in the African lungfish, Protopterus aethiopicus, by a combination of anatomical and physiological techniques. Particular emphasis was placed on mechanisms which operate under natural conditions in which air-breathing alternates with water-breathing. For such studies, awake, unrestrained fish were used after implanting devices for measuring blood pressure and flow. The results indicated that, despite ample anatomical opportunity for intracardiac mixing of the oxygenated and deoxygenated streams, in life the two streams were remarkably well separated. Also, using simultaneous pressure records from the consecutive cardiac chambers, the role of the pericardium in promoting venous return to the heart was clarified. On the basis of these observations, a hypothesis was formulated concerning the mechanisms by which the circulation is adjusted to the life habits of the lungfish, not only under its natural conditions as a water- and air-breather, but also during forced submersion and estivation.