AbstractPatients with classical European Kaposi's sarcoma were treated by intra‐ and peritumoral injections of human alpha leukocyte interferon (IFN) (12 cases) or, alternatively, with IFN and naturally synthesized IL‐2 (8 cases).All the patients were HIV negative with tumors which had been present for at least six months. In each patient, one tumor received 1 ml (50,000 IU) IFN alone or alternatively associated with 1 ml IL‐2 twice a week for 4–6 weeks; another nodule situated 10–12 cm away was considered as a control and remained uninjected. The clinical follow‐up revealed that, in the same patient in the same anatomical area, the treated nodule was cured in all the investigated cases; the untreated one was not. These data strongly suggest that IFN is the factor responsible for the involution and final cure of these Kaposi tumors treated by perilesional inoculations. Association with IL‐2 (and certainly also other interleukins) increases the beneficial clinical activation of the tumor involution.Histological examination showed that important histopathological changes occur in the treated nodules: complete disappearance of the Kaposi's aspect, fibrosclerous modifications progressively replacing the fibroblasts characteristic of Kaposi's sarcoma, abundant infiltrations of leukocytes, especially lymphocytes and necrotic patches, often with hemorrhagic centers. IL‐2 association seems to especially induce this last type of histolog