AIMS: to determine the effect of HLA-DPB1 status on rheumatoid arthritis (RA) susceptibility and disease expression. METHODS: HLA-DPB1 alleles were identified in 158 RA patients and 106 controls using PCR-sequence specific oligonucleotide probing. HLA-DPB1 allele frequencies were compared between patient and control groups and the strength of associations assessed using odds ratios and with 95% confidence intervals (CI). Associations observed in the total RA group were confirmed using a relative predispositional effect (RPE) analysis. RESULTS: an association between DPB1*0201 and RA was observed (OR 1.8, 95% CI 1.0-3.4). By contrast, negative associations were found with DPB1*0301 (OR 0.5, 95% CI 0.3-1.0) and DPB1*1101 (OR 0.06, 95% CI 0.001-0.5). These associations were confirmed using RPE analysis. On further analysis the increase in DPB1*0201 and decrease in DPB1*0301 frequencies in RA was found to be independent of DR4 status. The association of DPB1*0201 with RA appears to be most pronounced in male patients (OR 3.3, 95% CI 1.3-8.3), seronegative patients (OR 2.6, 95% CI 0.9-7.3) those with non-erosive disease (OR 2.6, 95% CI 0.9-7.3) or in patients with high titre antinuclear antibodies (OR 2.4, 95% CI 0.8-7.1). CONCLUSIONS: HLA-DPB1 alleles may be associated with the pattern of disease expression in certain RA patients and in some cases confer protection against disease.