HLA-DPB1 alleles were determined using the polymerase chain reaction and allele-specific oligonucleotide probes in Caucasoid patients with rheumatoid arthritis (RA) and in healthy controls. DPB1*0301 was found to be increased in seronegative patients (50.0% versus 10.8% in controls; relative risk = 8.3, P less than 0.0001). With our previous finding that DPB1*0301 is increased in seronegative children with polyarticular-onset arthritis, the results suggest a relationship between this disease and seronegative RA in adults.