We have established and characterized two new Kaposi's sarcoma (KS) cell lines derived from skin biopsies: AIDS-KSISTIV (from an AIDS-associated KS) and KSISTVIII (from a sporadic KS). AIDS-KSISTIV and KSISTVIII are composed mostly of spindle-shaped cells. They show similar patterns of immunohistochemical staining and are positive for smooth muscle (smooth muscle alpha-actin) and fibroblastoid (TE7) markers. Neither of these lines express the endothelial marker von Willebrand factor VIII. These immunohistochemical patterns are similar to numerous other KS lines that we and others have established. When seeded on a reconstituted basement membrane ("Matrigel"), AIDS-KSISTIV and KSISTVIII cells form branching colonies and invade into the Matrigel, as do other KS cultures that we have previously examined. This behaviour on Matrigel is similar to that of malignant sarcoma cells of different origin. The expression of vimentin and the morphology of the invasive colonies on Matrigel suggest that KS-derived cells are poorly differentiated mesenchymal cells. KS lesions are characterized by a conspicuous neovascularization, which appears to be derived from host cell recruitment. We tested the capability of the KS-cell supernatants to induce an angiogenic response in vitro. The new lines are able to stimulate human endothelial cell chemotaxis and invasion through Matrigel-coated filters. No differences in angiogenic potential in vitro were observed between the AIDS and the non-AIDS case, as we previously noted for other established cultures. Our new lines have the properties of true KS cells and confirm that KS spindle cells from HIV-positive or -negative patients have identical phenotypic and behavioural characteristics in vitro.