We have studied in eight rabbits the cardiovascular effects of midazolam, propofol and alfentanil with graded hypoxia. Central blood volume was reduced progressively by gradual inflation of a thoracic vena cava cuff so that cardiac index (CI) decreased at a constant rate. Under control conditions the haemodynamic response was biphasic. During phase I, mean arterial pressure (MAP) was maintained by a progressive decrease in systemic vascular conductance (SVCI). When CI had declined to a critical level, phase II occurred with an abrupt increase in SVCI and decrease in MAP. Phase I was prolonged by hypoxia, alfentanil and midazolam, but the effects were not additive. Phase I was shortened by propofol and this effect increased with hypoxia. The gradient of the SVCI response in phase I was also reduced by propofol > midazolam, but not by alfentanil. The occurrence of phase II was less frequent during alfentanil infusion than midazolam and propofol with all of the inspired gas mixtures. Thus the opioid was protective against circulatory collapse with hypoxia and simulated hypovalaemia.