1. The effects of moderate degrees of hypercapnia in hypoxia and in hyperoxia on the baroreceptor-cardiodepressor reflex have been studied in nine normal men.2. The beat-by-beat relation between pulse interval (I) and systolic pressure (P) during transient elevations of arterial pressure induced by intravenous injections of angiotensin II and phenylephrine was used to assess the sensitivity (DeltaI/DeltaP) and setting (I at a single reference arterial pressure) of the reflex.3. There was no consistent change in reflex sensitivity in any of the conditions studied.4. In hyperoxia (P(A, O2) approximately 200 torr) hypercapnia was associated with significant re-setting of the reflex in the direction of tachycardia. The extent of the re-setting was correlated with the degree of hypercapnia and with the accompanying increase in breathing.5. When hyperoxia with hypercapnia was replaced by hypoxia (P(A, O2) approximately 55 torr) with hypercapnia (which causes substantial arterial chemoreceptor activity), pulse interval at constant arterial pressure was further decreased.6. The tachycardia of hypoxia could not be accounted for by change of arterial pressure, P(A, CO2) or pulmonary ventilation, since it was most clearly demonstrable at constant values of pressure and either P(A, CO2) or ventilation.