Interest in the cell biology of antigen presentation is centered on dendritic cells (DCs) as initiators of the immune response. The ability to examine primary antigen-presenting cells, as opposed to cell lines, has opened a new window for study of antigen processing and peptide acquisition by Class II major histocompatibility complex (MHC) products, especially where intracellular trafficking of peptide-Class-II complexes is concerned. Here, we review the dynamics of Class II MHC-positive intracellular structures in dendritic cells as well as B cells. We focus on the generation of multivesicular bodies, where Class II MHC products acquire antigenic peptide, on the endosomal transport of peptide-loaded Class II MHC to the cell surface and on the importance of Class II MHC localization in membrane microdomains.