The relationship between depression and neuropsychological test performance in HIV-1 seropositive individuals is unclear. The present study was conducted to determine whether different patterns of neuropsychological test performance would be present in depressed vs. nondepressed individuals infected by the Human Immunodeficiency Virus (HIV-1). It was hypothesized that subjects evidencing depressed mood would demonstrate greater difficulty on measures of neuropsychological function. The subjects were 54 mostly symptomatic HIV-1 seropositive homosexual/bisexual males aged 20 to 60. A neuropsychological test battery together with the Beck Depression Inventory (BDI) was administered to all subjects. Stepwise multiple regression analysis revealed a significant relationship only between scores on the BDI and the Grooved Pegboard test and Trial 6 of the RAVLT. Subjects were then dichotomized using the BDI into high-BDI (M = 28.9) and low-BDI (M = 6.3) groups. Analysis of variance failed to reveal significant group differences between the depressed vs. the non-depressed groups on the neuropsychological measures despite their marked separation on the BDI. Similarly, examination of individual neuropsychological outliers again failed to demonstrate an increased number of outliers in the high- and low-BDI groups. These results suggest that the presence of clinically significant levels of depression in a non-elderly HIV-1 seropositive sample does not necessarily lead to significant neuropsychological dysfunction.