Immunotherapies using interferons and/or interleukins are currently the treatment of choice for metastatic renal cell carcinoma (RCC). Bone metastases and non-resectable local recurrence are negative predictors for successful immunotherapy and signs of poor prognosis. The present study was designed to evaluate the effectiveness of combined immunochemotherapy (ICT) and radiation therapy (RT) for bone metastases or local recurrence from RCC in a prospective fashion. From September 1997 to September 1999, 20 patients with progressive RCC were treated with a combination of RT and ICT [s.c. interleukin-2a (IL-2), s.c. interferon alpha (IFN-alpha) and i.v. 5-fluorouracil]. RT started in week 2 of ICT. The radiation field was limited to the symptomatic bone metastases (15 patients) or the local recurrence (five patients). The total dosages of the RT ranged between 45 and 50 Gy, administered in fractions of from 1.8 to 2 Gy daily. In case of objective response or stable disease, the patients received up to two further ICT courses. All patients had good pain relief. Three out of 20 achieved complete remission, three had a partial remission, nine were stable and five patients had progressive disease under the combined treatment. Median survival was 21 months, mean survival 24 months (range: 5-59 months). The side effects of the combined treatment are in the same range as with ICT alone (World Health Organisation grade 2 and 3). Of 20 patients, 19 had their pain medication reduced after treatment. The combination of ICT and RT is feasible. There is remarkable pain relief. Our data suggest that the combination of immunochemotherapy and radiation therapy may induce a synergistic antitumor effect for the treatment of bone metastases or local recurrence from RCC compared to data from the literature for ICT or RT alone.