Several studies have found weak associations between certain human leukocyte antigen (HLA) alleles and sarcoidosis, but none have been conclusive. Glutamic acid at position 69 in HLA-DPB1 has been reported to be strongly associated with chronic beryllium disease. The immunopathologic and clinical similarities between chronic beryllium disease (CBD) and sarcoidosis suggest that similar immune-response genes may be involved in susceptibility in both diseases. We analyzed the DNA sequence of HLA-DPB1 exon 2, which contains the hypervariable regions involved in binding antigens, in blood samples from African-American sarcoidosis patients and healthy controls. Results indicate that Val36 (odds ratio [OR] = 2.30) and Asp55 (OR = 2.03) are associated with increased risk for sarcoidosis, but no association with Glu69 was found. These results suggest that although HLA-DPB1 Glu69 is not associated with sarcoidosis, other alleles may make some contribution to susceptibility to sarcoidosis in African-Americans.