T cells proliferate in response to autologous non-T cells in the autologous mixed lymphocyte reaction (AMLR). AMLR was impaired in the peripheral blood of patients with advanced lung cancer (4,159 +/- 3,878 delta cpm vs. 11,221 +/- 4,156 delta cpm for normal donors) but normal or even higher in their malignant pleural effusions (13,257 +/- 7,075 delta cpm vs. 10, 870 +/- 5,013 delta cpm for nonmalignant control effusions). Blood T cells also failed to respond to autologous effusion non-T cells, while effusion T cells strongly responded to autologous erythrocytes blood non-T cells. The presence of blood T cells did not inhibit effusion AMLR of the same patients. A subset of T cells that form rosettes with autologous erythrocytes if found to proliferate in AMLR. The number of autorosette-forming cells was lower in blood T cells of cancer patients than in blood T cells of normal donors and in effusion T cells of the patients. After enrichment of autorosette-forming cells, there was no difference in AMLR of normal blood and cancer blood and effusions. These results indicate that the loss of AMLR in the blood of cancer patients is due to a reduction of number of autoreactive T cells and not to a defect of autologous stimulator non-T cells.