Involvement of the central nervous system (CNS) in patients with acquired immune deficiency syndrome (AIDS) is an increasing clinical problem. The most common brain complications are toxoplasmosis (50-70 per cent), primary CNS lymphoma (20-30 per cent) and progressive multifocal leucoencephalopathy (10-20 per cent). Almost two-thirds of these conditions can be treated, early diagnosis and therapy leading to survival with a good quality of life. Although clinical and neuroradiological criteria alone may have high predictive value, they are not sufficient to distinguish the broad spectrum of diseases reliably. Consequently, biopsy appears necessary for definite diagnosis in some cases. The potential role and timing of brain biopsy have been assessed. Twenty-four of 50 human immunodeficiency virus-seropositive patients with focal cerebral lesions were considered for biopsy between October 1991 and December 1992. Twelve underwent brain biopsy, seven stereotactic and five ultrasonographically guided. A diagnosis was achieved in 11 patients: six primary lymphoma, three progressive multifocal leucoencephalopathy, and one mycotic and one tuberculous abscess. Both techniques proved to be safe and reliable, with a 92 per cent diagnostic rate. These data confirm the usefulness of biopsy in patients with AIDS with its wide range of associated cerebral lesions that require different aggressive treatments. On the basis of this preliminary experience and reports in the literature, it is considered that brain biopsy is indicated for patients with focal enhancing cerebral mass lesions seen on computed tomography and magnetic resonance imaging who do not respond to an appropriate trial of empirical antitoxoplasmosis therapy and for those showing rapid clinical deterioration in whom imaging and serology do not suggest toxoplasmosis.