Typing at the HLA-DR locus was performed in 125 North American white patients with progressive systemic sclerosis (PSS). We could not confirm associations of PSS with the HLA-DR5 antigen or the HLA-B8/DR3 haplotype. A weak association of the DR1 antigen and PSS with diffuse scleroderma (27.5% vs 11.5% in local controls (corrected p less than 0.05) was observed. HLA-DR1 was significantly associated with the presence of anticentromere antibodies (p less than 0.05), and this combination was found more frequently in individuals with the CREST syndrome variant of PSS. This study failed to identify a clear-cut association between PSS and a genetic factor linked to the major histocompatibility complex.