Six patients with metastatic renal cell carcinoma were treated with five intravenous infusions (every other day) of autologous lymphocytes incubated in vitro with I-RNA extracted from the lymphoid tissue of guinea pigs immunized with the patient's own tumor. No toxicity was evident. One patient showed regression of multiple pulmonary metastases beginning three months after therapy with complete remission by six months. She remained without evidence of disease until 18 months after therapy. Two other patients had more than 50% regression of measurable metastases lasting eight and ten months after therapy. Two patients showed stabilization of previously growing renal cell carcinoma pulmonary metastases. A single patient with renal cell carcinoma metastatic to brain had progressive tumor growth after a single I-RNA treatment. Serial peripheral blood lymphocyte samples obtained from each of the patients during I-RNA therapy demonstrated progressive increase in in vitro cytolysis of allogeneic renal cell carcinoma targets. Boosts in cytolytic effect were shown in all patients during I-RNA treatment regardless of their subsequent clinical course. These results seem to justify a randomized, prospective trial of xenogeneic I-RNA therapy in renal cell carcinoma patients with lesser tumor burden.