A study of 26 families with multiple cases of RA was conducted in South West Ireland. In 149 relatives examined, 67 cases of RA were identified. An analysis of affected sibling pairs and trios revealed significant linkage between HLA and RA (p less than 0.05). A high frequency of DR4 was observed in probands (80.7 per cent) and affected members (74.6 per cent) compared with controls (18 per cent). An elevated frequency of the haplotypes A2-B44-DR4 (19.2 per cent) and A2-Bw62-DR4 (5.7 per cent) was seen in the affected sample. HLA-Bw62 was at raised frequency in probands (19.2 per cent) compared with controls (9 per cent). The haplotype frequency of A2-B44-DR4 was raised in affected females and A2-Bw62-DR4 in affected males. A low haplotype frequency of A1-B8-DR3 was found in all RA subjects. Disease severity (clinical and radiological criteria) was associated with DR4, but this did not reach statistical significance. A high incidence of extra-articular features of RA was observed, with DR4 occurring in all cases of vasculitis (75 per cent of whom were DR4 homozygous).