Our study investigates the nature of elevated depression scores on the MMPI-168 in human-immunodeficiency-virus- (HIV-)infected individuals. Comparison of MMPI scales, factor scores, and individual depression item endorsement rates were made between three groups of homosexual/bisexual men: asymptomatic HIV-1 seropositives (n = 156), symptomatic HIV-1 seropositives (n = 156), and a comparison group of HIV-1 seronegatives (n = 117). Elevated scores were found on the MMPI depression scale for all three groups, with HIV infection and the presence of symptoms being associated with significant elevations in depression. Analyses of these elevated scores through the use of factor scores and individual item analyses strongly suggest that endorsement of items related to physical symptoms and neuropsychological complaints accounted for much of the difference in overall depression scores between samples. Implications are discussed for measurement and diagnosis of depression in HIV populations.