Investigations on the effects of opioids on cerebrovascular dynamics have repeatedly demonstrated mild to moderate increases in cerebral blood flow velocity in the middle cerebral artery (CBFVMCA), cerebral blood flow, and cerebrospinal fluid pressure in humans and animals. However, the influence of hypocapnia on these fentanyl effects has not been investigated. We compared mean CBFVMCA during normo-and hypocapnia before and after administration of fentanyl (2.5 [mu] g/kg iv) in 20 awake humans. During normocapnia (end-tidal carbon dioxide [ETCO2] 40 mmHg) fentanyl significantly increased mean CBFVMCA (60+/-10 cm/s vs. 81+/-12 cm/s [mean+/-SD]; p< 0.01), whereas during hypocapnia (ETCO2 25 mmHg) mean CBFVMCA values were identical (40+/-7 cm/s vs. 40+/-7 cm/s) before and after fentanyl administration. These results confirm previous findings that administration of fentanyl increases CBFVMCA, but, more importantly, clearly indicate that hypocapnia reverses this potentially undesirable effect.