Two HLA class II beta-chain clones from a cell line homozygous for the DR1 haplotype have been characterized and sequenced. They represent a DR beta chain (2918.4) and a DQ beta chain (2918.8). Clone 2918.4 has been used to select mRNA from a lymphoblastoid cell line, and this was injected into Xenopus oocytes with mRNA selected with a DR alpha chain. The translation products were immunoprecipitated with a beta-chain-specific monoclonal antibody and electrophoresed on two-dimensional gels. This revealed positive signals in the positions predicted for beta and alpha chains. Sequence comparisons of 2918.4 with previously published DR beta-chain sequences confirm the presence of two regions of variability in the membrane distal domain. Analysis of the sequence of 2918.8 identified it as a DQ beta chain identical to one previously published from a DR3,w6 cell line. We speculate, therefore, that the DQ beta sequence represents the DQ1 specificity shared by the DR1 and DRw6 haplotypes.