Pediatric human immunodeficiency virus type 1 (HIV-1) infection is endemic throughout southern Africa. Neurologic complications are described in 20% to 60% of published series, mostly related to HIV-1 encephalopathy. With increasing HIV prevalence, more atypical cases are presenting. We present, as illustrative cases, seven children (three girls) with unusual neurologic sequelae as a consequence of HIV-1 infection. The median age at presentation was 33 months (range 7 months-6 years). Five of the seven children were developmentally normal before presentation. They presented with progressive multifocal leukoencephalopathy, myelopathy, intractable seizures, acute vasculitis and blindness, hemiplegia, peripheral neuropathy, and paraspinal lymphoma. Neuroimaging of the brain was performed in five patients, of whom one had basal ganglia calcification. All children had poor outcome with incomplete recovery or continued deterioration. In conclusion, children with HIV-1 infection who survive beyond the first year of life can present with a wide variety of neurologic complications. A similar spectrum of neurologic manifestations is likely to occur in other sub-Saharan African countries, characterized by high HIV prevalence. The case histories demonstrate that the neurologic features of pediatric HIV infection do not easily fit into a simplified classification system.