Recent observations have shown that plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) correlate with cardiac function or prognosis in heart failure patients. However, relatively little is known about changes in their plasma concentration during commonly occurring physiological states such as fatigue. Therefore, this study was designed to examine the physiological changes of plasma ANP and BNP concentrations using a chronic sleep-deprivation model. Bicycle ergometer cardiopulmonary exercise tests were performed in 10 healthy volunteers (mean age: 22.7 years). Blood samples for measuring ANP and BNP were drawn during the resting state and immediately after each exercise test. Cardiac output (CO) was measured during the exercise test by the impedance method. The study conditions were designed as follows: (A) a day following a period of normal sleep (control state) and (B) a day preceded by 1 month during which sleep lasted <60% of normal (chronic sleep-deprived state). Results were as follows. (1) Peak oxygen uptake and peak CO decreased during the sleep-deprived state compared with the control state. (2) There was no difference between peak heart rates measured during exercise under the 2 conditions. (3) Plasma ANP concentration during exercise increased significantly during the control state, whereas only a tendency toward increase was observed during the sleep-deprived state. (4) Plasma BNP concentration during exercise tended to increase in the control state compared with the resting state, whereas there was no difference in plasma BNP between after exercise and resting state in the sleep-deprived state. These results indicate that changes of ANP or BNP induced by exercise tended to be decreased by chronic sleep deprivation.