Data concerning the in vitro lymphocyte response against autologous tumors are reviewed, with a particular emphasis on melanoma. Evidence for such an immune response to tumors has been accumulating over the last 10 years through the work of several groups of investigators. Proliferative and/or cytotoxic responses are detectable in approximately 70% of patients with primary tumors, whereas the in vitro reaction with metastatic lesions is much less frequent. This response is mainly mediated by T lymphocytes obtained from peripheral blood, tumor lesions, and lymph nodes, but patients' suppressor cells and factors have been reported to inhibit such response. Clonal analysis revealed a low but consistent frequency of antimelanoma-specific T-cytotoxic and/or proliferating cells even in metastatic melanoma patients; such effectors are major histocompatibility complex restricted and use the T-cell receptor for tumor recognition of unique and, possibly, cross-reacting melanoma-restricted antigens. The chemical and genetic nature of such molecules remains to be defined. After the limited but biologically fundamental clinical responses achieved by adoptive immunotherapy with interleukin-2 and lymphokine-activated killers, T cells appear to lend themselves as crucial new effectors in adoptive immunotherapy of human cancer and, in particular, of melanoma.