Even though much is known about the presence of the common acute lymphoblastic leukemia antigen (CALLA) with respect to its distribution in hematopoietic and non-hematopoietic tissues, its functional role in lymphoid cells is as yet unknown. Given the fact that CALLA is completely modulated on the surface of lymphoid cells, we have employed pre-embedding immunogold techniques at electron-microscopical level and demonstrated that J5 monoclonal antibody (MoAb)-mediated modulation of CALLA expression on the lymphoblastic cell line NALM-6 is a specific, rapid process, closely resembling receptor-mediated endocytosis. Furthermore, it was found that CALLA was internalized through plasmalemmal pits and cytoplasmic vesicles and processed intracellularly in multivesicular bodies and secondary lysosomes. In contrast, HLA-DR antigen remained at the cell surface upon contact with specific MoAb. These data suggest that CALLA might be a receptor for a hitherto unknown signal molecule.