Double hemibody irradiation (DHBI) is an alternative treatment of stage III multiple myeloma (MM) in patients aged over 55 years. Toxic side-effects such as myelosuppression are a severe limiting factor to its use. We performed DHBI associated with human recombinant granulocyte-macrophage colony stimulating factor (hrGM-CSF) as support therapy in 10 patients with stage III MM to improve the tolerance to this treatment. Ten patients received subcutaneously 5 micrograms/kg/d of hrGM-CSF during 2 weeks after each course of hemibody irradiation. All these patients had stage III MM: eight previously received chemotherapy, six of them were regarded as patients with refractory MM and two with relapse. Two patients received DHBI as first-line treatment. hrGM-CSF increased safety and tolerance of DHBI. GM-CSF support reduced the mean time between upper body irradiation (UBI) and lower body irradiation (LBI): 41 v 108 d in a cohort of 32 patients previously treated without growth factor support. Overall there was no lethal infection with hrGM-CSF or granulocytopenia (5.0 x 10(9)/l v 0.4 x 10(9)/l at day 15 in patients without growth factor). hrGM-CSF also reduced stomatitis grading and thrombocytopenia (90 x 10(9)/l v 45 x 10(9)/l at day 15). Furthermore, hrGM-CSF increased blood colony forming unit-granulocyte macrophage (CFU-GM) and was well tolerated in all but one patient. hrGM-CSF reduces toxic side-effects of DHBI, thus providing an effective treatment in patients with advanced and resistant MM.