Based upon demonstration in our laboratory of repeated prevention of pulmonary metastases by adjuvant immune ribonucleic acid in animal preparations, xenogeneic immune ribonucleic acid was given in a phase I study to patients with advanced renal cell carcinoma. Six patients were treated with intravenous infusions of autologous lymphocytes incubated in vitro with immune ribonucleic acid extracted from splenocytes of guinea pigs immunized with the patient's own tumor. Serial peripheral blood lymphocytes were obtained during and after each treatment with immune ribonucleic acid for in vitro evaluation of cell-mediated cytolysis by 51chromium release assay and 125iodine iododeoxyuridine assay against allogeneic renal cell carcinoma targets and melanoma targets. Neither toxicity nor enhancement of tumor growth was observed. All patients demonstrated significantly increased cell-mediated cytolysis against allogeneic renal cell carcinoma targets but no change against melanoma targets. Increased cell-mediated cytolysis could be demonstrated in individual blood samples after incubation with immune ribonucleic acid. Further, progressive in vivo effect was demonstrated in in vitro assay of serial peripheral blood lymphocytes before each successive exposure to immune ribonucleic acid. Increased cell-mediated cytolysis persisted in peripheral blood lymphocytes up to 9 months after therapy. Although without controls 1 patient had complete response and 2 patients had partial responses (8 to 18 months). Two patients had stabilization of the disease for 3 to 4 months and 1 patient had progression of cerebral metastases. One patient is alive 24 months after therapy. These results would favor the institution of a randomized prospective trial in patients with advanced renal cell carcinoma or lesser tumor burdens.