An in vitro method for measuring changes in isometric force of vessels as small as 100 µm in outer diameter was used to determine whether the adrenergic mechanism of small pial arteries is the same as the large arteries of the circle of Willis. Fluorescence histology demonstrated the rich noradrenergic innervation of small branches of the middle cerebral artery. In spite of this rich innervation, contractile responses to transmural stimulation (TNS) were much smaller than maximum responses to histamine. An insensitivity to exogenous norepinephrine was shown which could account for this small response to TNS. In the presence of low concentrations of histamine, responses to TNS were increased. Thus, small pial arteries have characteristics similar to larger cerebral arteries.