Twenty patients with metastatic renal cell carcinoma and nine patients with minimal residual disease (MRD) but at high risk for recurrence following nephrectomy received weekly four milligram intradermal injections of purified RNA extracted from lymphoid organs of sheep immunized with human renal cell carcinoma. Eighty-six consecutive UCLA patients with metastatic renal cell carcinoma served as retrospective controls. Survival between subpopulations in each group matched by computer according to extent and location of metastases, age, sex, and interval between nephrectomy and occurrence of metastases were compared by Life Table Analysis. Survival was significantly greater in RNA-treated patients (P < .05) who had multiple metastases limited to the lungs when compared with matched controls. RNA therapy did not influence survival of patients with metastases to other sites (bone, brain, liver, lymph nodes, or skin) or multiple organ involvement. All nine MRD patients treated with RNA remained free of recurrence for a mean observation period of 18 months, range ten to 34 months. No significant toxicity was observed. Changes in skin test responses were related primarily to tumor burden. Increased lymphocyte mediated cytotoxicity in RNA recipients was associated with a somewhat improved survival period. Changes in absolute lymphocyte counts had no correlation with clinical course, and complement fixing antibody generally decreased after excision of tumor, was absent in patients with progression, and was present in low levels in patients with a favorable clinical response. RNA therapy may be of value in selected patients with metastatic renal cell carcinoma, and as an adjunct to definitive surgery.