Central nervous system involvement with AIDS is not uncommon. The indications and timing of brain biopsy remains controversial. Stereotactic CT-guided biopsy offers a safe and effective means of establishing a diagnosis in any patient with a cerebral mass lesion and has less morbidity and mortality than freehand biopsy or exploratory craniotomy. Eleven patients with AIDS have undergone CT-directed stereotactic biopsy between May 1987 and November 1990 with one death from intracerebral haemorrhage. Histological diagnosis of the biopsy specimens showed multifocal leucoencephalo-pathy, toxoplasmosis, lymphoma and non-specific changes. Biopsy is recommended for patients with an atypical presentation, negative serology, progressive clinical deterioration and differential response of lesions to empirical therapy.