In this article, we review the preliminary evidence for the activity of interleukin-12 (IL-12) against Kaposi's sarcoma (KS) and discuss these results in the context of the biology of IL-12 and KS. IL-12 is a cytokine that enhances type 1 immunity, induces production of interferon gamma (IFN-gamma), and mediates antiangiogenic effects. In addition, it can downregulate a constitutively active G protein coupled receptor that is encoded by Kaposi's sarcoma-associated herpesvirus, the causative agent of KS. These factors suggested that IL-12 might be worth exploring as a potential anti-KS agent. In an initial phase I pilot study, IL-12 was found to have anti-KS activity when used alone in patients with AIDS-associated KS who were on a stable regimen of antiretroviral therapy. In preliminary results from a subsequent study of the combination of IL-12 plus liposomal doxorubicin along with highly active antiretroviral therapy, remissions were obtained in a substantial percentage of patients with advanced AIDS-associated KS. IL-12 has also been found active in patients with certain lymphomas. These results suggest that IL-12 may be worth exploring further as a potential antitumor agent in selected tumors.