Infection with HIV-1 is associated with a 7000-fold increase in the incidence of Kaposi's sarcoma (KS). Some studies suggest that the risk of KS in HIV infection is increased with certain sexual practices and that a sexually transmitted agent could be involved. Exposure to this agent apparently alters both the morphology and growth regulation of the KS progenitor cells. These changes include the expression of the different cytokine receptors and the acquisition of autocrine growth loops. Perturbations of multiple cytokines during HIV infection, including oncostatin-M, interleukin-1 beta, and tumor necrosis factor-alpha, alter the subsequent growth of KS. These studies suggest that control of cytokine perturbations or the underlying HIV-1 infection could result in a significant reduction in the growth rate of AIDS-related KS.