The catecholaminergic innervation of cranial dura mater in humans was studied by examining several dural zones (vascular, perivascular, intervascular) in different regions (basal, calvarial, occipital, frontal, tentorial, parietal, temporal). The results demonstrate that catecholaminergic nerve fibers are present in human cranial dura mater and that these fibers, after exposure to formaldehyde vapors, show the specific fluorescence of catecholamines. There are more dural catecholaminergic nerve fibers in the basal region than in the calvarial region. Moreover, these nerve fibers are more abundant in the perivascular dural zone than in the intervascular zone. We hypothesize that these catecholaminergic nerve fibers may be involved in headache.