During cardiopulmonary bypass, haemodilution is standard practice and is accompanied by increases in cerebral blood flow (CBF). We investigated if changes in cerebral vascular resistance (CVR) during cardiopulmonary bypass-haemodilution are dependent on nitric oxide synthase. The cerebral response to haemodilution in nine dogs treated with the nitric oxide synthase inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME), was compared with a control group (n=8). Both groups underwent serial isovolaemic haemodilution (target packed cell volumes 0.39, 0.26, 0.19 and 0.14) using 6% dextran 70. CBF, CVR and cerebral metabolic rate for oxygen (CMRo(2)) were measured. While initial CVR was different in the two groups, haemodilution-dependent reductions in CVR were equivalent and the curves describing the packed cell volume-CVR relationship were parallel in control and nitric oxide synthase inhibition groups. Our data indicate that nitric oxide synthase does not play a primary role in the cerebral response to haemodilution.