CD8+ T cells have been shown to produce factors which modulate HIV-1 replication in both T cells and monocytic cells. Examination of the literature reveals that this modulation may occur by the production of -chemokines which block viral entry. However, another CD8+ T cell-derived activity targets the replication of HIV-1 at the level of transcription. CD8+ T cell factors strongly suppress replication and transcription in T cells and T cell lines, and in contrast, the factors enhance both replication and transcription in cells of the monocyte/macrophage lineage. The enhancement of transcription and replication by CD8+ T cell factors is induced by increased production of TNF by the macrophages. The enhancement is sensitive to pertussis toxin, indicating a G protein-coupled pathway. Thus, CD8+ T cells produce factors which mediate effects on transcription and replication of HIV-1 in a cell type-dependent manner. In this review a summary of the effects of chemokines and CD8-derived factors on HIV-1 transcription and replication is presented. The virus-host cell interactions that participate in the persistent replication of HIV in macrophages and the suppression of these functions in T cells require definition.The identification of CD8+ T cell factors which exert these controls on HIV-1 may lead to promising new therapies for HIV infection.