Sarcoidosis, in the United States, more commonly and severely affects African Americans. HLA associations with sarcoidosis have been reported, but most studies used case-control designs, which may produce biased results because of population stratification. We examined transmission of HLA-DQB1 alleles in 225 African American families with at least one offspring with sarcoidosis. Of five low-resolution HLA-DQB1 alleles, *02 and *06 showed significant deviation in transmission patterns to affected offspring. High-resolution typing of these allelic subsets revealed that HLA-DQB1*0201 was transmitted to affected offspring half as often as expected (p = 0.001), whereas DQB1*0602 was transmitted to affected offspring about 20% more often than expected (p = 0.029). Examining interactions between *0201 and *0602 alleles and environmental exposures showed that *0602 varied little with respect to exposure, but sarcoidosis risk associated with *0201 often depended on exposure status. Alternatively, the *0602 allele in affected probands was associated with radiographic disease progression, but the *0201 allele showed no significant correlation with phenotype. Major differences in the amino acid sequences encoded by *0201 and *0602 alleles exist, which may explain the differential effects these alleles have on sarcoidosis susceptibility and progression in African Americans.