To determine the activity of sequential administration of thymopentin (TP-5), interferon alpha-2a (IFN) and interleukin-2 (IL-2) in metastatic renal cell cancer (RCC), 17 patients with RCC were treated with TP-5 50 mg/d on days 1 to 14, IFN 3 MIU/d on days 14, 15, 21, 22 and IL-2 18 MIU/d on days 16 to 20, and 23 to 27. Treatment was given subcutaneously and cycles were repeated every 6 weeks. All patients were assessed for toxicity and response. No objective responses were observed. Two patients had a short-lived disease stabilization. Median survival was 9 months. Toxicity was generally moderate. The most important side-effects were related to IL-2 administration. In view of the lack of antitumor activity, the combination of TP-5 + IFN + IL-2 in the doses and schedule used in this trial cannot be recommended. The investigation of chemotherapeutic and immunological agents that can effectively synergize with IFN or IL-2 is essential.