✓ Bicompartmental analysis for the calculation of regional cerebral blood flow (rCBF) from 133Xe clearance in brain tissue has not been thoroughly explored in clinical studies. Most authors rely either on the average rCBF obtained by height/area analysis of the clearance curves or on the initial-slope flow index. Possibly the reason is that the validity of the bimodal flow distribution in abnormal brain tissue is considered questionable. In the present study, bicompartmental analysis, performed by a least-square computerized iterative approach, was used in the calculation of the flow and weight of the tissue of the brain of patients with severe head injuries. The analysis was found to give important information of the nature and course of the brain lesions even if the clearance curves did not have the normal bi-exponential shape, provided the results obtained were properly interpreted. In such cases, the values of the flow and relative weight could not be taken as flow and weight values of gray and white matter, but rather as indices of fast and slower flow components. The interpretation of the results was based on the identification of three types of 13-minute clearance curves, each being characteristic of a type of brain lesion. The clearance curves from fairly normal brain tissue appeared to be bi-exponential; curves from areas of severe cortical contusion had, in addition, an initial and rapid “third” component, a tissue peak, whereas curves from severely edematous brain tissue approached the monoexponential shape.