1. Our aim was to determine the role of nitric oxide (NO) in regulating cerebral blood flow (CBF) in foetal sheep under conditions of both hypoxaemia and normoxaemia. 2. Aseptic surgery was performed on 11 pregnant sheep at 125 +/- 1.1 days of gestational age (g.a.) when foetal vascular catheters were implanted for the measurement of CBF using coloured microspheres. Additionally, each ewe was prepared for one of two procedures for inducing foetal hypoxaemia; either an adjustable clamp was placed around the maternal common internal iliac artery to reduce uterine blood flow, or a catheter was implanted into the maternal trachea for insufflation of N-2. At 131 +/- 0.3 days g.a., in control foetuses (n = 5), CBF and cerebral vascular resistance (CVR) were measured under basal (normoxaemic) conditions and after 3 h of hypoxaemia, In other foetuses (n = 6) CBF and CVR were measured under basal conditions and after 3 h of hypoxaemia; in these foetuses NO synthesis was inhibited with N-nitro-L-arginine (NOLA) between 2-3 h of hypoxaemia. 3. In the hypoxaemia experiments foetal SaO2 and PaO2 were reduced (P<0.05) in both control and NOLA-treated foetuses, from normoxaemic values of 69.5 +/- 2.1% and 23.8 +/- 1.0 mmHg, respectively, to 29.3 +/- 1.0% and 14.6 +/- 0.4 mmHg during the period of hypoxaemia. In control foetuses, CBF (mL/min) was increased by 82.7% during hypoxaemia; in NOLA-treated foetuses CBF increased by 55.3%, which was less (P<0.05) than in control foetuses, In control foetuses CVR (mmHg/mL/min) was reduced by 43.5% during hypoxaemia, whereas in NOLA-treated foetuses there was no significant change. 4. In five of the 11 foetuses, the role of NO in regulating CBF under basal (normoxaemic) conditions was determined at 132 +/- 0.3 days g.a. Cerebral blood flow and CVR did not significantly change from basal values after NOLA treatment. 5. We conclude that in foetal sheep NO plays an important role in regulating cerebral vascular tone and hence CBF during hypoxaemia, but its contribution during normoxaemia is less apparent.