Antinuclear antibodies were demonstrated in the sera of 43 of 45 (96%) patients with progressive systemic sclerosis (22 of 24 with diffuse scleroderma and 21 of 21 with the CREST syndrome variant). This high percentage of positive reactions resulted from the use of a tissue culture substrate (HEp-2) to detect antinuclear antibodies by the indirect immunofluorescent method. Patterns of nuclear staining included diffuse fine speckles, large coarse speckles, nucleolar and centromere staining. When organ sections such as mouse kidney were used as substrate for the detection of antinuclear antibodies, nucleolar staining and centromere staining were the two patterns most frequently overlooked. Three types of antibodies appeared to be highly specific for scleroderma: antibody to Scl-70 antigen, antibody to centromere, and antinucleolar antibody. The anti-centromere antibody appeared to be highly selective for the CREST variant of progressive systemic sclerosis.