This study sought to determine if human immunodeficiency virus-type 1 (HIV-1) infected depressed men were more likely to be neuropsychologically impaired than their nondepressed counterparts. Subjects were 47 HIV-1 infected men who met DSM-III-R criteria for current major depressive disorder (MDD) and 47 HIV-1 infected nondepressed male controls (M age = 34.2 years) equated on HIV-1 disease severity, demographics, and drug use. The psychiatric interview included the Structured Clinical Inventory for the DSM-III-R, and Hamilton Rating Scale for Depression. The neuropsychological battery included tests covering 8 functional domains based on an expanded Halstead-Reitan Battery. The medical assessment included a history and physical examination, immunologic staging, and evaluation of prescription and recreational drug use. Prevalence of global neuropsychological impairment in the two groups (depressed vs. control) did not differ [53% vs. 38% respectively; chi 2(1, N = 94) = 2.11, p > .05]. While syndromically depressed patients performed less well than nondepressed individuals on memory tests [delayed retention portions of the Story Memory Test: F(1,91) = 5.34, p < .05; and Figure Memory Test: F(1,90) = 4.16, p < .05], the majority of depressed participants (64%) did not have clinically impaired memory. No relationship between neuropsychological impairment and severity of depression was observed. The results suggest that, while HIV-1 infected men with major depression may perform more poorly than nondepressed men on some aspects of memory tasks, they are not more likely to evidence clinically significant neurocognitive impairment.