Objective. To test the hypothesis that the calcium antagonist diltiazem is effective in the treatment of calcinosis.Methods. Diltiazem, 240-480 mg/day, was given to 4 patients with idiopathic or CREST-related (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias) calcinosis for 1-12 years. Serial radiographs of the affected areas, using identical technique, and clinical evaluations were obtained. A fifth patient, who did not tolerate diltiazem, received verapamil, 120 mg/day for 18 months.ResuZts. All patients taking diltiazem had a reduction or disappearance of the calcific lesions, with striking clinical improvement. One patient's case was followed for 12 years. The response to diltiazem during the first 5 years of treatment has been previously reported in detail; however, over 7 years of additional treatment, there was further reduction of the lesions. One patient developed a large calcific lesion while receiving verapamil for hypertension, and after verapamil was replaced with diltiazem, there was a dramatic response. Verapamil was ineffective in the fifth patient, who did not tolerate diltiazem.Conclusion. Long-term treatment with diltiazem, but not verapamil, is effective in calcinosis. Submitted for publication March 27, 1995; accepted in revised form June I , 1995. mary and secondary hyperparathyroidism, sarcoidosis, and hypervitaminosis D. In these patients correction of the underlying condition usually leads to a reduction in calcification. The other group includes conditions characterized by normal calcium and phosphate metabolism, such as connective tissue diseases (scleroderma, CREST syndrome [calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias], systemic lupus erythematosus, and polymyositis), and are known as calcinosis or dystrophic calcification (1). Calcinosis may also be idiopathic. The process typically involves mineral accumulation within matrix vesicles and sometimes within mitochondria (2). Deposits of calcium salts are formed in the extracellular space and often drain to the exterior as a whitish, thick material. This drainage occurs intermittently without significant reduction in the size of the calcific masses.The factors that ultimately lead to the formation of calcium deposits are poorly understood, and no reliable therapy for calcinosis is currently available. Systemic administration of steroids is generally ineffective (3,4); intralesional administration of steroids appears to produce some benefit in calcinosis confined to the skin (5,6). Chelating agents, such as disodium EDTA (3,4), and diphosphonates (7,8), have yielded unimpressive results in clinical trials. In a few patients, probenecid (9,lO) and colchicine (1 l) have appeared to be beneficial. More recently, low-dose warfarin therapy was advocated for mild cases of calcinosis universalis (12,13), but it was ineffective for more advanced cases (14).We have reported the arrest and radiographic regression of multiple lesions in a patient with calcinosis...