Focal intracerebral lesions were biopsied stereotactically in 23 adult HIV-infected patients, the main indication for which was the failure to respond to anti-toxoplasma treatment. A cerebral disease was the initial or main complaint in 19 of them. In 22 of 25 stereotactic approaches, a clear-cut morphological diagnosis could be established (9 primary brain lymphoma, 7 necrotizing toxoplasma encephalitis, 5 progressive multifocal leukoencephalopathy, 1 HIV encephalitis, 3 unspecific tissue changes). In 7 of 8 deceased patients, autopsy confirmed the bioptical diagnosis. The high diagnostic yield was related to the strategy of the stereotactic method and the sample size (3 to 4 consecutive samples along the stereotactic track including the marginal zones, 1 cm long tissue cylinders). Formalin fixation and paraffin embedding of the samples provide the possibility of serial sections and special stainings (immunohistochemistry, in-situ hybridization) and kill the HIV. Stereotactic brain biopsy is a highly accurate diagnostic tool to ascertain the nature of focal intracerebral lesions in selected AIDS patients.