There is strong evidence that patients with AIDS have loss of cortical neurons. In this study we have examined the hippocampus of rhesus monkeys infected with simian immunodeficiency virus (SIV) to determine whether neuronal damage occurs in this model of human AIDS and to investigate its time course. Twenty-eight infected monkeys (23 young [< 9 years] and five elderly [> 16 years]) were compared with 11 controls (six young and five elderly). Numbers of nucleolated neurons per unit area of section and mean pyramidal cell diameters were measured in each CA sub-field of each animal. There was neuronal atrophy in all regions examined, as early as 3 months following inoculation. An initial apparent increase in neuronal density at 3 months did not reach statistical significance. In younger animals, however, there was a later, significant association between the reduction in neuronal density and duration of infection. Elderly animals were only examined at a single, early time point. These results show that there is neuronal pathology following infection with SIV and that there is probably subsequent neuronal death.