Anticentromere antibody (ACA) was found in the serum of 4 (3%) of 120 patients with progressive systemic sclerosis with diffuse scleroderma and in 69 (49%) of 141 with progressive systemic sclerosis with the CREST syndrome variant. The 69 CREST syndrome patients with ACA were compared with the 72 CREST syndrome patients without ACA. The former were older at the onset of symptoms and significantly more frequently female (97% versus 78%, P less than 0.01). Those with ACA more often had telangiectasiae of the digits (93% versus 75%) and calcinosis (55% versus 22%). These differences were also present after the groups were stratified according to duration of disease. Cutaneous involvement was similar in both degree and extent in the 2 groups; 20% of CREST patients both with and without ACA had forearm skin thickening. Pulmonary interstitial fibrosis on chest roentgenogram and restrictive disease on pulmonary function testing were significantly less frequent in the ACA patients. Gastrointestinal involvement, pulmonary arterial hypertension, and cardiac abnormalities were similar in both groups, and there has been no difference in survival between CREST syndrome patients with and without ACA. Tissue typing studies revealed a significant association between ACA and HLA-DR1.