In 46 patients with rheumatoid arthritis (RA) the allele C4B*3 occurred in 6 patients, while among 350 normal controls, it occurred 6 times (P less than 0.00002). Among 9 white and 1 black families, each of which had 2 or more members with RA, there were 36 haplotypes associated with RA. An extended haplotype (specific HLA-B, DR, complotype haplotypes in significant linkage disequilibrium) containing C4B*3: HLA-B15, DR4, BF*S, C2*C, C4A*3, C4B*3, was found twice (P less than 0.001) among whites with the disease-associated chromosomes.