Human B cell alloantigens were studied by two-dimensional gel electrophoresis. The heavy (alpha) and light (beta) chains precipitated by xenoantisera were compared on B lymphoblastoid cell lines of different HLA-DR types. In accordance with the results of other investigators, we observed considerable electrophoretic variability of beta subunits. Significant electrophoretic differences between alpha subunits isolated from different cells were also observed through the use of a pH 5 to 7 gradient in the isoelectric focusing dimension. HLA-DR allelic products from a heterozygous line exhibited differences in beta subunit electrophoretic mobility but apparent identity of alpha subunits.