Fifteen patients with widespread painful osseous metastases from breast cancer unresponsive to other systemic therapy were treated with mithramycin at dose levels usually used for treating Paget's disease. Ten patients had relief of pain, which was marked and rapid in onset in seven. Mobility was greatly improved in four patients. Healing of bone lesions did not occur and new lesions developed while treatment was being given. Clinical response was associated with a decrease in plasma alkaline phosphatase. Toxicity was mild and consisted of nausea in most patients and a slight decrease in platelet count in one patient. Mithramycin is a useful agent for palliation of painful bone metastases and should be considered for further trials of combination chemotherapy for advanced breast cancer with bone metastases.