There is still controversy concerning which patients with asymptomatic carotid stenosis or symptomatic moderate stenosis are likely to benefit from carotid endarterectomy. The surgical candidates for carotid endarterectomy should have a high risk for stroke, but a low risk for operative complications. Therefore, new effective patient selection strategies, including haemodynamic testing, schemes of risk stratification and pre-operative cardiac testing, are under investigation. To improve haemodynamic assessment of patients with carotid artery stenosis, we evaluated a novel global cerebral blood flow (CBF) heterogeneity index at rest and after acetazolamide injection in patients undergoing carotid endarterectomy. CBF heterogeneity index was measured in 15 patients by using basal and acetazolamide enhanced 99mTc-HMPAO SPET both before and 1 month after surgery. CBF heterogeneity index was calculated as the coefficient of variation of a total of 44 cerebral regions representing mainly both ipsi- and contralateral grey matter. A high linear correlation was observed between CBF heterogeneity index and ipsilateral carotid stenosis degree (r=0.74, P=0.003). Before surgery, CBF heterogeneity index increased significantly after acetazolamide injection when compared to the basal condition (from 7.0+/-1.5 to 8.3+/-1.7%, P=0.008). This response disappeared after carotid endarterectomy. When compared to pure asymmetry of CBF (ipsi/contralateral CBF ratio), the CBF heterogeneity index seemed to reflect, more sensitively, the haemodynamic effects of carotid endarterectomy. The CBF heterogeneity index after acetazolamide injection is a sensitive marker of the haemodynamic consequences of carotid artery stenosis and its operative treatment.