We studied the dynamic profile of respiratory and circulatory activities during sustained isocapnic hypoxia in healthy males. In response to end-tidal PO2 depression to about 55 Torr, minute ventilation first increased briskly and then depressed. Such biphasic response to hypoxia was also observed in the heart rate. A significantly positive correlation was found between the magnitudes of ventilatory and heart rate responses. No significant increases were found in arterial noradrenaline and potassium, but adrenaline significantly increased gradually with time. Furthermore, when VT and f were intentionally maintained constant so as to prevent the biphasic ventilatory change, the biphasic heart rate response previously seen in spontaneous hypoxic breathing disappeared. We suggest that the heart rate is mainly determined by the pulmonary vagal inflation reflex. Putative neurochemicals to elicit hypoxic ventilatory depression, and arterial catecholamine and potassium concentrations may not be directly related to the specific profile of the biphasic heart rate response during moderate hypoxia.