We explored the possibility that neurologic and neuropsychological changes constitute the earliest detectable manifestations of human immunodeficiency virus (HIV) infection. Without knowledge of HIV status, we assessed neurologic signs and symptoms and administered a battery of neuropsychological tests to 208 homosexual men, of whom 84 were HIV negative, 49 were HIV positive and asymptomatic, 29 were mildly symptomatic, and 46 had significant medical symptoms but not the acquired immunodeficiency syndrome. There was no difference between the HIV-negative and HIV-positive men in the frequency of neurologic signs or of defective or borderline performance on any neuropsychological test. However, HIV-positive men performed slightly but significantly worse than HIV-negative men on tests of verbal memory, executive function, and language. Similar results were obtained when comparisons were limited to HIV-positive medically asymptomatic and HIV-negative men. There was no degradation of neurologic status or neuropsychological performance across stages of HIV severity, but neurologic and neuropsychological summary scores correlated with CD4/CD8 ratios in the HIV-positive group. Ratings of neurologic signs and symptoms correlated with neuropsychological summary scores in the HIV-positive group only. Cognitive complaints were more frequent in the HIV-positive men; they correlated with actual test performance in the HIV-positive but not HIV-negative men. The constellation of subjective and objective neuropsychological and neurologic findings suggests the possibility of a definable syndrome associated with HIV infection in asymptomatic individuals.