Human normal non hematopoietic cells of mesenchymal and neuroectodermal origin may express functional IL-Rs. For instance, in these cell types, IL-2 can stimulate proliferation (endothelial, intestinal and nervous cells) or modify the expression of adhesion molecules (fibroblasts) or inhibit proliferation (bone marrow stromal cells). Therefore, some cytotoxic effects described during IL-2 biotherapy could be due to a direct interaction between IL-2 and non-hematopoietic tissues. The expression of functional IL-2-R has also been reported in several human cell lines derived from solid tumors. In some instances IL-2 inhibits cell growth (head and neck, gastric and renal carcinomas), but in other tumors, growth stimulation and increased expression of markers of tumor progression have been reported (intestinal, breast, and lung carcinomas, gliomas, fibrosarcomas and melanomas). Additionally, secretion of biologically active IL-2 has been reported in some melanoma and breast cancer cell lines. Transcripts for the novel cytokine IL-15, which utilizes the beta and gamma chains of the IL2-R, have been found in melanoma cells and anti-IL-15 mAbs inhibit HLA class I expression in these cells. Therefore these cytokines may modify, inside a tumor, the behavior of both stromal and neoplastic cells. All these data may have important implications in our understanding of tumor host interactions and in future strategies of immunotherapy.