The CREST syndrome is a variant of systemic sclerosis characterized by the presence of calcinosis. Raynaud's phenomenon, esophageal motility abnormalities, sclerodactyly and telangiectasia. The serums of 27 patients with the CREST syndrome have been examined for the presence of antinuclear antibodies. Twenty-six of 27 (98 percent) serums contained high titers (> one:80) of an antibody that produces a discrete speckled pattern of immunofluorescence on a human laryngeal carcinoma cell line (HEp-2). The antibody has been shown to react with the centromeric region of metaphase chromosomes. This antibody was also found in three of 14 patients with Raynaud's disease, in one of 60 patients with systemic lupus erythematosus, in three of 26 patients with systemic sclerosis with diffuse scleroderma and in one of 15 patients with mixed connective tissue disease. The antibody was not detected in the serums of patients with rheumatoid arthritis. Sjögren's sicca complex or linear scleroderma. Patients with osteoarthritis who were age- and sex-matched to the group with the CREST syndrome did not have anticentromere antibodies. Autoantibodies found in other connective tissue diseases (anti-DNA, anti-RNP, Sjögren's syndrome antigen B (anti-SS-B) were not found in serums from patients with the CREST syndrome. A case report illustrating the appearance of the anticentromere antibody at a time when Raynaud's phenomenon antedated the clinical diagnosis of CREST syndrome is presented.