The HLA antigens were determined in 54 Caucasoid patients with scleroderma (ARA criteria). All were assessed for extent of skin and organ involvement, anticentromere (ACA), and scleroderma 70 (Scl 70) antibodies. The antigens DR1, DR3 and DR5 were raised in the patient group, and DR2 was lowered. Of these only the increase in DR5 was significant (χ2 = 5.2; p = 0.02). The increased frequency of DR3 was attributable to a rise in the Al, B8, DR3 haplotype (χ2 = 3.9; p = 0.05). Patients with non-diffuse disease showed a significant increase in the DR1 and DR5 antigens (χ2 = 3.7, p = 0.05; χ2 = 8.0, p = 0.01). No association was found between the HLA antigens and specific organ involvement. Anticentromere antibodies were present in 15 of the HLA-DR typed patients. Thirteen of these 15 patients were either DR1 or DR5. No relationship was found between the frequencies of HLA antigens and anti-Scl 70 antibodies.