The monoclonal antibodies 7.3.19.1 (anti-DRw52-like) and B8.11.2 (anti-DR framework) were used for the isolation and characterization of HLA class II molecules expressed by HLA-DR3 and DR5 homozygous B cell lines. Sequential immunoprecipitation studies demonstrated that from these cells class II molecules can be isolated which are characterized by the presence or absence of DR framework (DR) and DRw52-like (DRw62) determinants: (DR+, DRw52+), (DR+, DRw52-) and (DR-, DRw52+). The DR3 donor cells appeared to express only the (DR+, DRw52+) and (DR-, DRw52+) class II molecules whereas DR5-positive cells express only the (DR+, DRw52+) and (DR+, DRw52-) class II molecules. Besides qualitative differences some of the above-mentioned molecules appeared to differ in their levels of expression. To investigate whether this might have functional implications, cells with the HLA-DR3 and -5 haplotypes were used to present antigen purified protein derivative of tuberculin (PPD) to PPD-specific T cell lines and the blocking capacity of the two monoclonal antibodies 7.3.19.1 and B8.11.2 was determined. A remarkable correlation was observed between the type of class II molecule blocked by these monoclonal antibodies and its quantitative expression. However, (DR-, DRw52+) molecules, clearly expressed by DR3 cells, were not involved in the presentation of PPD. This indicates that not only quantitative but also qualitative aspects may play a role in the selection of the type of class II molecule that will be involved in antigen presentation.