Cleavable cell surface radiolabelling reagents were used to measure the endocytosis and recycling of class II major histocompatibility complex (MHC) glycoproteins in human B-lymphoblastoid cells. It is shown that mature class II αβ dimers on the cell surface are constitutively endocytosed and that recycling can be demonstrated even from small endosomal pools. Endocytosis was blocked when cellular ATP levels were depleted or when clathrin polymerization was inhibited, implicating clathrin-coated pits in the endocytic process. Taken together with earlier studies, these results suggest that mature class II MHC molecules are constitutively endocytosed and recycled from acidic peripheral endosomes which may enhance their capacity to bind and pre...