Light and moderate exercise elevates the regional cerebral blood flow by approximately 20% as determined by ultrasound Doppler sonography (middle cerebral artery mean flow velocity; MCA V(mean)). However, strenuous exercise, especially in the heat, appears to reduce MCA V(mean) more than can be accounted for by the reduction in the arterial CO(2) tension (P(a)CO(2)). This study evaluated whether the apparently large reduction in MCA V(mean) at the end of exhaustive exercise relates to an enhanced cerebrovascular CO(2) reactivity. The CO(2) reactivity was evaluated in six young healthy male subjects by the administration of CO(2) as well as by voluntary hypo- and hyperventilation at rest and during exercise with and without hyperthermia. At rest, P(a)CO(2) was 5.1 +/- 0.2 kPa (mean +/- SEM) and MCA V(mean) 50.7 +/- 3.8 cm s(-1) and the relationship between MCA V(mean) and P(a)CO(2 )was linear (double-log slope 1.1 +/- 0.1). However, the relationship became curvilinear during exercise (slope 1.8 +/- 0.1; P < 0.01 vs. rest) and during exercise with hyperthermia (slope 2.3 +/- 0.3; P < 0.05 vs. control exercise). Accordingly, the cerebral CO(2) reactivity increased from 30.5 +/- 2.7% kPa(-1) at rest to 61.4 +/- 10.1% kPa(-1) during exercise with hyperthermia (P < 0.05). At exhaustion P(a)CO(2) decreased 1.1+/- 0.2 kPa during exercise with hyperthermia, which, with the determined cerebral CO(2) reactivity, accounted for the 28 +/- 10% decrease in MCA V(mean). The results suggest that during exercise changes in cerebral blood flow are dominated by the arterial carbon dioxide tension.