The reliability of blood flow velocity measurements performed using transcranial Doppler sonography was investigated with regard to the intra- and inter-observer variability. We compared the flow velocity values recorded in the intracranial vessels by two experienced investigators both under rest conditions and during hypercapnia induced by an apnea test. The results showed how flow velocity values measured at the level of the middle cerebral artery, anterior cerebral artery, ophthalmic artery and basilar artery were not significantly influenced by intra- or inter-examiner variability. The flow velocity increases recorded from the middle cerebral artery during the activation test proved to be reproducible when the measurements were repeated by the same examiner, but more variable when detected by different investigators. On the basis of the available data, the clinical relevance of transcranial Doppler results must take into account the degree of reliability of its measurements.