Kaposi's sarcoma (KS) is a multifocal neoplasm of unknown origin. All forms of KS are composed of spindle-shaped cells with elongated nuclei and sheets of endothelial-like cells. The proliferation of spindle cells is accompanied by the presence of an inflammatory infiltrate composed predominantly of T-cells. It has been suggested that this infiltrate might consist of a virally stimulated clonal population of T-lymphocytes which can produce growth factors initiating and substaining the proliferation of spindle-shaped cells. In this study we analyzed for clonal T-cell receptor gama gene rearrangements the T-cell populations present in the cutaneous infiltrate of seven cases of classical Kaposi's sarcoma using a polymerase chain reaction-based approach. Our data demonstrate the lack of a significant clonal population of T-cells in the cutaneous infiltrates of KS. This finding is indicative of a reactive polyclonal response of T-cells to the spindle-shaped cells and supports the contention that spindle-shaped cells are pathogenetically the central cell type in the disease. Our data also indicate that the anti-KS T-cell response, being polyclonal in nature, does not result from clonal expansion of T-cells targeting tumor-associated antigenic peptides.