Dendritic cells (DCs) are postulated to be involved in transmission of human immunodeficiency virus (HIV) type 1 to T cells and in stimulation of HIV-1–specific cell-mediated immunity. Blood DCs have been categorized as myeloid (mDC) and plasmacytoid (pDC) subsets, on the basis of differences in phenotype and function. Blood DC subset numbers and expression of costimulatory molecules and HIV-1 coreceptors on DCs were measured in the blood of treated and untreated HIV-1–infected subjects and uninfected control subjects. Absolute numbers of mDCs and pDCs were lower in HIV-1–infected subjects than in control subjects, most significantly in those with active HIV-1 replication. Increased surface expression of costimulatory molecules was observed on both DC subsets in subjects with HIV-1 viremia. Highly active antiretroviral therapy suppression of plasma viremia resulted in increases in blood DC numbers and decreases in DC costimulatory molecule expression. These findings further define the impact of HIV-1 replication on blood DC subsets in vivo