Human immunodeficiency virus type 1 (HIV1) is neurotropic. One of the morphological changes that is seen in patients with acquired immunodeficiency syndrome (AIDS) is cerebral atrophy affecting various structures including the neocortex. The cause of atrophy is not known. The total number of neocortical neurons was estimated in formalin fixed brains of 12 males with AIDS and 12 male controls matched for age and height. The mean number of neocortical neurons was 16.0 x 10(9) (coefficient of variation = 0.11) in the AIDS patients compared with 21.9 x 10(9) (coefficient of variation = 0.22) in the controls, a difference of approximately six billion (p < 0.005, 2-tailed). The global neuronal loss was 37%, and affected all four neocortical lobes. Ten patients did not have a history of central nervous system symptoms; two patients had a history of dementia. The number of neurons in the AIDS cases was not associated with dementia. AIDS is the first disease in which a global loss of neocortical neurons has been demonstrated using unbiased stereological methods. The loss of more than one third of the neurons may partly explain the cortical atrophy. Focal neuron loss has been reported by several authors, but none have been based on unbiased methods. In this group of AIDS patients the severe loss of neurons did not correspond to neurological deficits.