The relationship between duration of illness and neuropsychological performance was examined in 25 asymptomatic HIV-infected men with an estimated date of seroconversion. Mean duration of illness was approximately 2 years. After controlling for CD4 level at the time of neuropsychological examination, duration of illness was correlated with measures of visual attention, mental flexibility, dexterity, auditory information processing, and response fluency, as well as an overall measure of neuropsychological performance. Although these patients performed within normal limits, these data suggest that duration of infection may be related to subtle alterations in neuropsychological performance. These results are discussed with regard to possible mechanisms that implicate gradual accumulation of neurotoxins.