Dendritic cells (DC) are highly potent activators of the immune response. The precise mechanisms that give rise to the DC phenotype are not known. To investigate the mechanisms that contribute to the generation of the DC phenotype, precursor DC were freshly isolated from human blood and allowed to mature in vitro. These matured DC showed the phenotypical and functional characteristics of DC. Analysis of the MHC class II and invariant chain (li) biosynthesis revealed that upon maturation, class II synthesis was induced whereas ii synthesis was significantly up-regulated. In mature DC, despite the presence of large amounts of ii, export of MHC class II molecules from the endoplasmic reticulum was incomplete, up to 4 h after biosynthesis. Thus, MHC class II-ii synthesis and transport in DC is highly regulated during maturation of DC. Analysis of the regulatory mechanisms may contribute to a better understanding of antigen-presenting capacities during the differentiation of DC.