Early-stage lesions of Kaposi's sarcoma (KS) are composed of single-layered, highly flattened cells lining collagen bundles, whereas late-stage lesions contain densely packed, spindle-shaped cells. We examined the progression of KS lesions in oral mucosa and lymph nodes from patients with AIDS, using antibodies specific for blood vascular endothelial cells (Factor VIII-related antigen) and their basement membrane (Type IV collagen and laminin). In addition, the plant lectin Ulex europaeus, which selectively stains blood vessels, was also used. In early-stage KS lesions, fibronectin, laminin and Type IV collagen were co-distributed at the interface between KS cells and collagen bundles; Factor VIII-related antigen and Ulex europaeus lectin staining was present in vascular channels and in the KS cells. However, in late-stage lesions, few if any KS cells stained with antibody to Factor VIII-associated antigen, although endothelial cells lining blood vessels were positive. Strong staining for laminin and Type IV collagen was present in a pericellular pattern throughout the nodular late-stage lesions. Since lymphatic capillary endothelium does not produce basement-membrane-specific macromolecules, these results support the conclusion that KS cells are related to blood vascular endothelium but eventually lose certain endothelium-specific markers as the cells are transformed into the spindle-shaped cell type.