We describe a distributed parameter (DP) model for tracer kinetic analysis in brain and validate the derived perfusion values with positron emission tomography (PET) scans. The proposed model is applied on actual clinical cases of hemispheric stroke. Nine patients with experienced transient ischaemic attack or minor stroke and a stenosis of the internal carotid artery were referred for computed tomography (CT) and PET imaging. The applicability of the DP model in clinical practice was tested in seven patients with acute stroke who received a baseline perfusion CT study and a noncontrast follow-up CT study after 2.4+/-1.8 days. The mean blood flow (F) value for all patients with carotid stenosis in the pooled data (54 regions of interest (ROIs)) was 37.9+/-11.2 mL/min per 100 g in perfusion CT and 35.6+/-9.8 mL/min per 100 g in perfusion PET imaging [r=0.77 (P=0.00)]. Regression analysis of the pooled ROIs for every patient revealed significant correlation between F values in seven patients [r=0.50 to 0.79 (r(2)-values ranged from 0.45 to 0.79), (0.01 < or = P < or = 0.05)]. Parametric maps that corresponded to all physiologic parameters were generated for every perfusion CT in the patients with acute stroke using the DP model. The ischaemic area was better delineated in F, intravascular blood volume and lag time (t(lag)) maps. The correlation coefficient comparing the visually outlined regions of abnormality between the t(lag) parametric map and the follow-up CT scans was 0.81 (P=0.003). In conclusion, DP physiological model using more realistic pharmacokinetics is feasible in dynamic contrast-enhanced CT of the brain in patients with acute and chronic cerebrovascular disease.