Analysis of HLA DRB1 and DQB1 Bam HI RFLPs revealed four DRB1 (4.8, 5.2, 6.0 and 7.0 kb) fragments and a 3.2 kb DQB1 fragment to be significantly increased in Caucasians with seropositive RA compared to healthy individuals. The 4.8, 5.2 and 7.0 kb DRB1 fragments were found in 86.5% of RA patients and in 56% of the controls (p = 10−3, relative risk (RR) = 5.0), while the 6.0 kb fragment was found in 79% of RA patients compared to 32% of controls (p = 2× 10−5, RR = 8.0). The 3.2 kb DQB1 fragment was observed in 63.5% of RA patients versus 38.0% of controls (p = 10−2, RR = 2.8). Analysis of these fragments relative to HLA phenotypes revealed that the 4.8, 5.2 and 7.0 kb DRB1 fragments were strongly correlated with DR4, −7, −9 and −w53 serotypes, the 6.0 kb RFLP with DR4 and the 3.2 kb DQB1 fragment with DR1 and DQwl. Using probes specific for the 5′ or 3′ regions of the DRB1 gene, the 5.2 and 6.0 kb DRB RFLPs were mapped to the 5′ end and the 4.8 and 7.0 kb RFLPs to the 3′ end of the DRB1 gene. A probe generated from the second exon of the DRB4 (DRw53) gene recognized only the 5.2 and the 6.0 kb RFLPs corroborating the 5′ location of these RFLPs. Family studies further confirmed that these RFLP's segregated with HLA phenotypes. Copyright © 1989, Wiley Blackwell. All rights reserved