IFN-gamma mRNA levels were measured in unstimulated PBMC and purified cell subpopulations, utilizing branched DNA assays, to characterize the cell type(s) that contribute to the in vivo increase in IFN-gamma gene expression seen in HIV infection. PBMC and CD8 T cells from HIV-seropositive subjects (HIV+) showed 2.5-fold increases in mean IFN-gamma mRNA levels compared to HIV-uninfected subjects (HIV-). Within individuals, CD8 T cells showed the highest IFN-gamma expression regardless of HIV status, which suggests that HIV infection enhances the IFN-gamma gene expression in CD8 T cells rather than inducing a shift to and/or increasing expression of IFN-gamma mRNA in other cell types. HIV+ subjects with increased PBMC IFN-gamma mRNA had elevated plasma levels of HIV RNA, neopterin, and beta 2-microglobulin. No differences in IFN-gamma mRNA levels were seen among HIV+ stratified by CD4 T cell number. Increased IFN-gamma may result from or be a contributing factor to increased viral load.