Assessing the adequacy of collateral circulatory pathways has become increasingly important in the investigation of cerebral circulation. Using transorbital Doppler ultrasonography (TOD), we examined the ophthalmic artery (OA) in patients with hemodynamic significant internal carotid artery (ICA) occlusive disease. The velocity and the direction of flow in the OA were studied in 45 patients (occlusion n = 27, stenosis > 75% n = 18), and in 30 age matched controls, under baseline conditions and within 30 minutes after the i.v. administration of 1 g acetazolamide as a vasodilatory stimulus. Based on the direction of flow before and after acetazolamide, the 45 patients could be separated into four groups with increasing degree of ICA lesions. In group I the OA flow was anterograde, but the velocity decreased after acetazolamide. In group II the OA direction became retrograde after acetazolamide, indicating collateral flow to the brain. In patients with retrograde OA flow following acetazolamide injection (group II-IV), the vessel reacted similarly to an intracranial artery, with marked increase in velocity when vasoreactivity was tested. TOD and the acetazolamide test provide useful information about potential collateral OA flow to the brain in patients with ICA occlusive disease.