Regulation of HLA class II transcription is complex, with both locus-specific and allele-specific polymorphisms associated with consensus regulatory region promoter elements. In order to evaluate the potential function of allele-specific elements, HLA-DQB1 transcripts and in vivo footprinting of the DQB1 promoter were studied in human cell lines inducible for HLA class II expression. In the heterozygous melanoma cell line Me9229/18, differential expression was observed for two DQB1 alleles. This variation was reflected in both steady-state and inducible transcripts, although methylation patterns of the promoter elements were similar for both alleles. This in vivo allelic difference expression, which correlates with previous studies of in vitro reporter gene transcription, indicates the potential for functionally important differences in tissue-specific and inducible expression attributable to promoter region polymorphism in HLA genes.