In addition to opportunistic infections, neoplasms or cerebrovascular complications, metabolic encephalopathies are a classical cause of diffuse brain dysfunction in HIV infection and are frequent in the terminal stage. We report an HIV-infected patient with symmetrical, focally increased signal in the midbrain on proton density-and T1-weighted MRI without corresponding high signal on T2-weighted images or on CT. While the precise nature and cause of this uncommon finding is not fully understood, the available evidence suggests that these lesions might represent a novel metabolic encephalopathy.