In volunteers, hyperventilation improves autoregulation. However, in head-injured patients, hyperventilation-induced deterioration and improvement of autoregulation have been reported. We have re-examined this question using an index of pressure reactivity. Thirty patients with severe or moderate head-injury were studied. Arterial blood pressure, cerebral perfusion pressure (CPP), and intracranial pressure (ICP) were recorded over 20 minute epochs separated by ten minutes of equilibration at baseline and during moderate (>3.5 kPa) hyperventilation. End-tidal CO2 was constant during each phase of data acquisition. Pressure reactivity was assessed using an index 'PRx' based on the response of ICP to spontaneous blood pressure changes. Hyperventilation decreased PaCO2 from 5.1 +/- 0.4 to 4.4 +/- 0.4 kPa (p < 0.0001). ICP decreased by 3.7 +/- 2.2 mmHg (p < 0.001). CPP increased by 5.9 +/- 8.2 mmHg (p < 0.001). Overall, PRx did not change significantly with hyperventilation. However, there was a significant negative correlation between baseline PRx and the change in PRx (r = -0.71, p < 0.0001). This suggests that patients with disturbed pressure-reactivity may improve, whereas patients with intact pressure reactivity remain largely unchanged. Our data suggest that the response of pressure reactivity to hyperventilation is heterogeneous. This could be due to hyperventilation-induced changes in cerebral metabolism, or the change in CPP.