Introduction: Pulmonary metastases of renal cell carcinoma (RCC) are associated with poor prognosis. Inhalation therapy with interleukin-2 (IL-2) is thus an appealing method for palliation. This multicenter study summarizes the national experience of IL-2 inhalation in patients with lung metastases of RCC. Patients and methods: Forty patients (median, 66.5 years of age) with radiologically documented progressing pulmonary metastases were enrolled. All patients had to be able to comply with inhalation technique, and were not candidates for other treatment options. Twenty-eight patients were systemic treatment-naive. The protocol included three daily inhalations of IL-2 to a total dose of 18 MU. Treatment had to be continued until one of the following occurred: progression; a complete response; a life threatening toxicity; or patient refusal. Response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) system. Results: The disease–control rate reached 57.5%, with a partial response rate of 2.5% and a disease stabilization rate of 55%. Median time to progression was 8.7 months. The main side-effects were cough and weakness. Conclusions: Inhalation of IL-2 for the treatment of pulmonary metastases in RCC is feasible, tolerable and beneficial in controlling progressive disease for considerable periods of time. The definition of response of biological therapy may need to be re-assessed and modified: stable disease should be regarded as a favorable