We developed control system of total artificial heart (TAH) during exercise simulating the circulatory response of natural heart. The following procedures were taken to develop this system. 1) Measurement of hemodynamics and physical activity rate (PAR) of natural heart goats during treadmill exercise. 2) Estimation of cardiac output from PAR using a non-linear model. 3) Development of a pneumatic artificial heart (AH) driver with high speed controllability and a control unit to deliver CO calculated from PAR beat by beat. 4) Evaluation of the physiological condition of the TAH goat during exercise controlled by this system. Using this control method, CO of TAH goats was similar to that of natural heart goats during treadmill exercise. Hypertension was observed during exercise. This hypertension was considered to be derived from two causes. One was high inflow and outflow resistance of cannulae between AH pump and living body. The other was the disorder of peripheral circulatory control mechanism in TAH animal. Such as increased sympathetic activity, insufficient secretion of atrial natriuretic polypeptide (ANP) and decreased sensitivity of peripheral circulatory system with ANP.