Twenty-five families with probands who have rheumatoid arthritis (RA) were studied for clinical evidence of disease and for HLA status. This confirmed an association between RA and DR4 in 19/25 probands (76 per cent, p = 0.008). These 19 probands carried 24 haplotypes which contained DR4. There was no significant increase of DR4 haplotypes bearing B15(Bw62) or B44 when compared with published control haplotype data. The rare complement allele C4 B3 was detected as part of the extended haplotype A2 Cw3 B15(Bw62) DR4 C4 A*3B*3 in three probands with severe RA. Further studies to examine disease severity and autoantibody expression are in progress.