Thirty human immunodeficiency virus (HIV) infected individuals entered a longitudinal study without signs of dysfunction of the central nervous system (CNS). Nine of these individuals developed a systemic illness between study visits, and 7 of these 9 patients (78%) had neurological signs at the next examination (e.g., action-intention tremors, abnormal gait, release signs, abnormal deep tendon reflexes). Only 2/21 (9.5%) of the subjects who did not develop systemic illness showed such signs. These data are consistent with the hypothesis that other factors (e.g. cytokines) as well as the HIV may cause subtle CNS dysfunction.