The pattern of autonomic deficit in the face of cluster headache patients resembles the deficit in patients with a postganglionic sympathetic lesion from some other cause; however the presence of abnormal cardiac rhythms and bilateral pupillary reflex deficit in some patients with cluster headache suggests that the lesion might compromise central sympathetic drive. To investigate this possibility, the vasomotor and sudomotor startle reflex was investigated in the hands of sic cluster headache patients with ocular and thermoregulator signs of postganglionic sympathetic deficit in the face; for comparison, responses were also investigated in 15 patients with a lesion in the cervical sympathetic pathway from some other cause. The startle reflex was intact in the hands of the six cluster headache patients, but was diminished ipsilaterally in patients with a central or preganglionic sympathetic lesion and also, surprisingly, in patients with a postganglionic lesion caused by an aneurysm of the internal carotid artery. Ocular sympathetic deficit was greater in patients with an aneurysm of the internal carotid artery than in cluster headache patients or in patients with a postganglionic sympathetic lesion from some other cause; the aneurysm may have compromised neurons with projections to the face and hand, or could have induced transsynaptic degeneration of preganglionic fibers supplying both regions. The findings indicate that central sympathetic drive is not impaired in cluster headache patients; thus, a peripheral lesion probably induces sympathetic deficit on the symptomatic side of the face.