Kaposi's sarcoma (KS) is a mesenchymal tumor of unclear etiopathogenesis. The epidemic form of KS occurs in up to 30% of HIV-infected individuals with lesions that have mixed cellularity, spindle cell proliferation, and neoangiogenesis. Although not completely defined, the spindle cells, thought to be the tumor cells of KS, are of mesenchymal cell origin, with features resembling endothelial and smooth muscle cells. The establishment of in vitro and in vivo model systems (AIDS-KS cell culture and the transgenic mouse model) for KS have allowed studies of the pathogenesis of KS. In particular, studies of the biologic characteristics of the AIDS-KS cells have demonstrated the presence of autocrine and paracrine growth activities. The findings of specific cytokines produced by the AIDS-KS cells may explain the histologic changes found in the KS lesion. Similarly, the development of KS-like lesions by inoculating cultured AIDS-KS cells into nude mice suggests that KS is an inducible disease. Finally, the results obtained in tat-transgenic mice and the proliferative induction of AIDS-KS cells by addition of exogenous (cell-released or recombinant) Tat protein suggest that this HIV gene product may have an important role in the development or progression of KS in HIV-infected individuals.