1. Eight conscious rabbits were repeatedly subjected to progressive reduction in central blood volume by gradually inflating a thoracic inferior vena caval-cuff so cardiac index (CI) fell at a constant 8.5% of baseline/min. 2. Caval-cuff inflations were performed after 10 min exposure to 100, 21, 12-14 and 8-10% O2, with and without the addition of 3-4% CO2, in randomized order. 3. The haemodynamic response to progressive reduction in central blood volume was biphasic. In Phase I, systemic vascular conductance index (SVCI) fell linearly, supporting mean arterial pressure (MAP). When CI had fallen to a critical level, Phase II occurred in which SVCI rose abruptly, MAP plummeted and respiratory drive progressively increased. 4. During Phase I, there were independent linear relationships between PaCO2 (but not PaO2) and the rates at which SVCI and MAP changed during the progressive fall of CI. The higher the level of PaCO2, the greater was the rate of fall of SVCI and the less the rate of fall of MAP. 5. There was an inverted U-shaped effect of PaO2 on the level of CI at which Phase II occurred: (a) during hyperoxia (100% O2), Phase II occurred later than during normoxia (21% O2); and (b) across the normoxic and hypoxic gas mixtures (21-8% O2, with and without added CO2), there was an independent linear relationship between PaO2 (but not PaCO2 or PaO2 x PaCO2) and the level of CI at which Phase II occurred. That is, the lower the level of PaO2, the later was the onset of Phase II. This interaction is best explained by an increased level of central sympathetic vasoconstrictor drive during hypoxia.