The cluster diathesis. We present further evidence for a sympathetic defect of vasomotor control of the anterior cerebral artery (ACA) on the side of the headache during cluster periods. In 119 cluster headache patients, utilizing transcranial Doppler, we measured CO2 reactivity of the major intracranial vessels, in and out of cluster. Reactivity was significantly lower during the cluster period, but only in the ACA on the side of the headache. Nineteen patients followed sequentially for a full cycle (ie/both in and out of a cluster period) showed the same changes. In 3 out of 6 patients in an active cluster period, we describe a lesion on Gallium single-photon emission computerized tomography (SPECT) in the region of the cavernous sinus which fades as the patient moves out of cluster. It is felt that this lesion may represent the cavernous sinus plexus lesion postulated as the central lesion in cluster. Changes in the sympathetic outflow at this point could explain the changes we have described in ACA CO2 reactivity during cluster. 