Despite advances in imaging of the brain, an accurate diagnosis of brain lesions requires tissue sampling and histological verification. A series of CT-directed procedures has been performed in 300 patients with deep sited, multiple, diffuse, extensive, small or inflammatory lesions, brain stem haematomas and tumours presenting with epilepsy. A positive diagnosis was obtained in 271 cases (92.8%), no diagnosis in 21 cases (7.2%). Therapeutic results were also obtained in eight cases (2.7%) of brain stem haematoma aspiration. Complications occurred in 14 cases (4.7%) including one death (0.3%). Because of the importance of an accurate diagnosis in order to avoid inappropriate therapy, together with the relative safety of the technique, CT-directed stereotactic biopsy should be considered in all patients harbouring deep seated, multiple, diffuse, small or inflammatory brain lesions.