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Circulatory responses to administration of carbon dioxide were determined in 41 awake human volunteers during controlled or spontaneous respiration. Compared with spontaneous respiration (Paco2, 37 torr), controlled respiration (Paco2 36 torr) was associated with a significantly lower cardiac index and stroke index but with an increased total peripheral resistance which maintained constant arterial blood pressure. When exogenous CO2 was administered during either controlled or spontaneous respiration (range 39 → 50 torr), cardiac index, heart rate, stroke index, indices of myocardial contractility, and forearm blood flow all increased significantly, while total peripheral resistance decreased significantly. These data serve as reference points for measurements of cardiovascular function in normal man, and for studying the modification of the circulatory response to CO2. Anesthetic agents, drugs, and disease states which alter autonomic tone in either direction may modify the response.