The cell-mediated immune (CMI) response to tumor-associated antigens present in 3 M KCL extracts of renal cell carcinoma tissue was measured in patients with renal cell carcinoma (RCC) by the leukocyte migration inhibition (LMI) test. Of 30 patients with histologically proved RCC, 19 (63%) gave a positive LMI test; whereas, 2 of 28 (7%) of the normal donors, 13 of 43 (30%) patients with other cancers, and 5 of 14 (36%) benign kidney disease patients gave positive tests. Thirteen per cent of RCC patients reacted to a normal kidney extract. Although 33% gave a positive response to a lung carcinoma extract, the incidence of reactivity was less than that observed with the lung cancer patients. These results suggest that a CMI response to a renal carcinoma-associated antigen was measured by the LMI test. Correlation of the LMI data with the stage of disease and clinical status indicated that 71% of patients that had a localized tumor and were clinically free of disease one year postnephrectomy lost their tumor-directed CMI response. Patients with distant metastasis (Stage D) were LMI positive provided they had not received radiation or hormone therapy at the time of testing. These results suggest that the demonstration of CMI, as measured by the leukocyte migration inhibition test, correlates with the presence of active disease.