Individual responses of cerebral blood flow to acetazolamide are highly variable. We hypothesized that this may be due to interactions with cardiovascular diseases and medication. Therefore, we measured the haemodynamic effects of acetazolamide in patients with various cardiovascular disorders and evaluated whether these had any correlation with calculated cerebral perfusion reserve. Ten male patients aged 58 +/- 9 years (mean +/- S.D.) were studied with first-pass radionuclide ventriculography and echocardiography before and 20 min after the administration of 1 g acetazolamide. Systolic blood pressure fell from 133 +/- 21 to 128 +/- 19 mmHg (P < 0.05) and the cardiac output to total blood volume ratio increased from 0.85 +/- 0.18 to 0.92 +/- 0.11 (P = 0.05), indicating a 14% reduction in peripheral vascular resistance. In a further study, 15 patients aged 60 +/- 7 years (22 studies) were studied simultaneously with a nuclear stethoscope and 99Tc(m)-hexamethylpropyleneamine oxime single photon emission tomography before and after acetazolamide administration. The cardiac output ratio increased from 0.81 +/- 0.17 to 0.89 +/- 0.17 (P < 0.05) and showed a significant inverse correlation with calculated cerebral perfusion reserve. In conclusion, acetazolamide increases the cardiac output ratio and reduces systolic blood pressure, indicating reduced peripheral vascular resistance in patients with various cardiovascular diseases and medication. The increase in the cardiac output ratio is inversely related with calculated cerebral perfusion reserve. This helps to explain the high individual variability in calculated cerebral perfusion reserve.