Kaposi's sarcoma (KS) is a complex neoplasm comprising spindle cells, vascular structures, erythrocytes, and an inflammatory infiltrate. The pathogenesis of this disorder is not yet understood, which is a major impediment to the design of safe and effective new therapies. We previously reported a murine model in which simian virus 40 (SV40) T-antigen-transformed murine endothelial cells induce lesions with the histopathologic features of KS. We have now cloned by limiting dilution seven morphologically distinct tumor-derived lines, all of which express the SV40 T antigen. Because SV40 is non-permissive in mouse cells, the presence of this viral marker permits definitive identification of cellular origin. We report here that both spindle cell and epithelioid cell clones from these KS-like tumors are derived from endothelial cells.