By the application of separation techniques in a stepwise manner to mechanically prepared cell suspensions from human tumour biopsies it has been possible to isolate tumour cells having high viability and low contamination with host cells. These tumour cells have been used as targets in 51Cr release cytotoxicity assays using autologous lymphocytes from blood or lymph node as effectors. It has been possible to investigate this reactivity in 30 patients with malignant and four patients with benign tumours. Significant autologous cytotoxicity in the blood lymphocytes was detectable in two of 12 lung tumours, nine of 18 other carcinomas and sarcomas but in none of the benign cases. Cytotoxicity was not limited by the presence of obvious residual disease at the time of operation although reactivity was less frequently detectable in patients with secondary involvement. Reactivity in the tumour-draining lymph nodes largely paralleled that in the blood in the limited number of patients examined. The technical problems encountered during this study and the role of natural cytotoxicity in the interpretation of these data are discussed.