An international study to investigate the role of human leukocyte antigen (HLA)-DPB alleles in Hodgkin's disease was conducted with 17 participating centers in 12 countries. A total of 741 patients and 686 controls were typed using polymerase chain reaction amplification of HLA-DPB alleles and subsequent sequence specific oligonucleotide hybridization. The frequency of HLA-DPB1*0301 was found to be significantly increased in white patients, compared with ethnically matched controls. In this population group, the DPB1*0301 allele is associated with a relative risk of 1.95 (P < 0.01). There was also a significant reduction in the frequency of HLA-DPB1*0401 in patients from Japan and Taiwan (relative risk, 0.15; P < 0.01). Clinical analysis from data on 551 patients demonstrated a significantly inferior remission duration in patients with HLA-DPB1*0901, overall (P < 0.05), and in the Japanese and Taiwanese populations (P = 0.02), where this allele is most prevalent. This analysis suggests an epidemiological as well as a possible prognostic association between HLA-DPB alleles and Hodgkin's disease.