Changes in cardiovascular homeostasis after injury are mediated by tissue damage and not haemorrhage. During treatment of the injured patient it is assumed that the cardiovascular responses follow recognized physiological principles. Studies in humans have shown that injury causes a profound suppression of arterial baroreflex function which alters the normal relationship between heart rate and blood pressure and casts doubt on this assumption. To investigate the mechanism of baroreflex suppression, we have studied the effects of the two major components of injury, blood loss and tissue damage, on baroreflex function in healthy volunteers. Baroreflex function was assessed using suction stimulation of the carotid sinus. The loss of 500 ml blood had no effect on baroreflex sensitivity. A human laboratory model of tissue injury reduced the ability of the baroreflex to compensate for a rise in blood pressure (P less than 0.05, Wilcoxon signed rank test). We conclude that tissue damage, rather than hypovolaemia, appears to mediate the effect of injury on baroreflex function in the injured. Blockade of neural signals from damaged tissue may have a role in the treatment of injury. 