Samarium-153-EDTMP is an effective agent for palliation of widespread skeletal metastases because it concentrates in bone metastases which have an osteoblastic component. Similar concentration in areas of osteoblastic activity in ankylosing spondylitis, Paget's disease and rheumatoid arthritis suggests a possible new treatment approach. Three patients with ankylosing spondylitis, one patient with Paget's disease and one patient with rheumatoid arthritis were treated with 153Sm-EDTMP. Objective and subjective improvement was noted, especially in ankylosing spondylitis patients. Samarium-153-EDTMP has disease-modifying potential in ankylosing spondylitis and Paget's disease and has palliative value in resistant rheumatoid arthritis. Further trials to determine optimal dose, treatment scheduling, long-term disease-modifying potential and toxicity are needed.