The histologic nature of deep-seated intracranial lesions can be determined by using a computer-assisted stereotactic biopsy technique. The procedures are performed with use of local anesthesia. A data base consisting of stereotactic computed tomographic scans and stereotactic cerebral angiography is acquired. Target coordinates and trajectory approach angles are calculated by using a computer system in the operating room. Since July 1984, 36 patients with a variety of pathologic lesions in various intracranial sites have undergone this procedure at our institution. Of the 36 patients thought to have neoplastic lesions preoperatively, 6 were found to have nonneoplastic lesions, information that was of importance in the therapeutic management of these patients. Of the 30 patients with tumors, 24 had astrocytomas of various grades, 3 had metastatic lesions, and an additional 3 had lymphomas. Computer-assisted stereotactic biopsy with arteriographic control is an accurate and relatively safe method of determining the histologic nature of any suspicious intracranial lesion.