Eighteen asymptomatic HIV-1-infected (HIV+) individuals were evaluated neuropsychologically before and during Interferon Alfa-n3 treatment. All 18 were evaluated twice, and 9 were evaluated three times. Analyses revealed few significant effects of treatment on cognitive, motor, and affective function. Improvements occurred over visits on measures of attention and appeared to reflect practice effects. Decrements occurred over visits on measures of procedural and supraspan learning. Examination of the data suggested that decrements were due to procedural artifacts and were not medication effects. In contrast to prior studies reporting significant neuropsychiatric side effects of interferon alpha treatment, few such effects occurred when HIV+ individuals were treated with Interferon Alfa-n3 and were evaluated neuropsychologically in a systematic manner.