Studies on immunotherapy with inhaled interleukin-2 (IL-2) for the treatment of pulmonary metastases in renal cell carcinoma patients have indicated objective response rates of 11%. The aim of the present study was to evaluate efficacy, toxicity, and quality of life during inhaled immunotherapy with IL-2. Patients with pulmonary metastases of renal cell carcinoma were treated with interferon-alpha (IFN-alpha) 3 x 10(6) IU/m(2) s.c. on days 1, 3, and 5 and inhaled twice a day 9 x 10(6) IU IL-2 on days 1-5. Treatment continued for 4 weeks and after a 2-week rest a second cycle was given. Patients who responded received two additional cycles. Quality of life was assessed according a self-administered quality of life questionnaire (QLQ-C30) before, during, and after therapy. Of 23 treated patients, 21 could be evaluated concerning response rate and toxicity [16 men, 5 women; median age: 60 years (38-72 years)]. Sixteen patients had pulmonary metastases only and five patients additionally had bone or liver metastasis or local recurrence. One patient (5%) developed a partial remission for 4 months and ten patients (47.5%) showed a stable disease for a median time of 6 months (2-24 months). The median follow-up was 9 months (3-26 months). Ten patients (47.5%) developed progressive disease. Maximal toxicity was mild and grade III-IV toxicity (WHO) was not observed. The patients' quality of life did not change significantly at any time during therapy. Inhaled immunotherapy is a treatment option with little toxicity, but achieved only a few objective responses. Whether or not it influences overall survival could not be answered in this study.