Atrophy and white matter changes seen on magnetic resonance imaging scans have been observed in association with the acquired immunodeficiency syndrome dementia complex, but these appear to be late findings relative to clinical expression. We report a new magnetic resonance imaging observation in patients with early cognitive impairment due to human immunodeficiency virus infection. Fifty-two patients had a total of 86 magnetic resonance imaging scans during the study period. All scans were obtained with a 1.5-T system. The proton density spin echo (repetition time of 2000 milliseconds and echo delay time of 30 milliseconds) study demonstrated high-signal lesions in the region of the splenium of the corpus callosum and in the crura of the fornices. The lesions demonstrated no contrast enhancement with gadopentate dimeglumine. Pathological examination was performed in five patients. The fornix-subcallosal abnormality may be related to the memory dysfunction in patients with human immunodeficiency virus-related cognitive impairment.