Fifty-eight unrelated patients with familial (36) and non-familial (22) rheumatoid arthritis (RA) have been studied for HLA-A, B, C, and DR antigens. Among the 36 probands of families with multiple cases of RA (Group I) 73 per cent are DR4 positive, and 60 per cent of the DR4 negative probands possess DR1. The corresponding frequencies among the 22 patients with non-familial (sporadic) RA (Group II) are 59 per cent and 56 per cent, respectively, DR4 and/or DR1 are present in 89 per cent of patients in Group I and 82 per cent in Group II. Homozygosity for DR4 has been definitely established by family studies in six of the 26 DR4 positive patients (23 per cent) in Group I, and a further two patients are possible homozygous. Family studies have not been performed in sporadic RA patients but two of 13 DR4 positive patients in this group are possibly homozygous for DR4. HLA haplotypes A1, Cw7, B8, DR4; and A2, Cw3, B15, DR4 are shared by two or more unrelated probands of multicase families.