Human immunodeficiency virus (HIV) infection of the brain causes a complex cascade of cellular events involving several different cell types that eventually leads to neuronal cell death and the manifestation of the AIDS-associated dementia complex (ADC). Upon autopsy HIV-infected individuals show lesions within subcortical regions of the brain, including the cerebellum. Previously we have demonstrated, in primary and cell culture models of rat and human astrocytes, a change in intracellular pH (pH(i)) due to increased Na(+)/H(+) exchange following exposure to inactivated virus or gp120, the major HIV envelope glycoprotein. To further investigate whether any such in vivo pH(i) changes occur in human brains subsequent to HIV infection, we measured the pH(i) of the cerebellum in eight HIV-positive individuals and nine healthy volunteers using (31)P magnetic resonance spectroscopy imaging (MRSI) at high field strength (4.1 T). The results showed a significant difference between the age-adjusted mean pH(i) in the cerebellum in control group and patient groups (7.11 +/- 0.03 vs 7.16 +/- 0.04), and further HIV-infected individuals displayed a significant increase in the number of cerebellar volume elements that were alkaline. We hypothesize that this propensity towards alterations in cerebellar pH(i) may portend later neurological involvement resulting from HIV infection.