The contribution of neurotransmitters known to be present in the cervical sympathetic nervous system to cerebral autoregulation was evaluated in the anaesthetised cat using a continuous measurement of cerebral cortical perfusion with laser Doppler flowmetry and an in vitro pial vessel preparation. Autoregulation was tested by venesection and fluid administration to achieve changes in blood pressure from -40% of resting control levels to +80% and flow was monitored. Between -20% and +50% there was no significant alteration in cortical blood flow with perfusion following blood pressure passively outside these ranges. The non-competitive neuropeptide Y antagonist PP56 shifted the level at which the change in flow was passively dependent on blood pressure from +60% to +38%. The pial vessel study demonstrated that PP56 shifted the dose-response curve for the vasoconstrictor effect of NPY with a maximal reduction of 22 +/- 6%. These data suggest that the cervical sympathetic nerves with NPY play an active role in cerebral autoregulation. Furthermore in view of the longer time course of action of neuropeptide Y, it is an ideal transmitter candidate to be involved in cerebral autoregulation and any compound that blocks its action must be considered to potentially alter the normal cerebrovascular physiology.