The CD1 family of polypeptides is divided into two groups, the CD1b and CD1d group. Both groups are involved in stimulation of T cell response. Molecules of the CD1b group can present Ag derived from bacterial cell walls to T cells; the process of Ag acquisition is thought to take place in endosomes. Little is known about Ag presentation by CD1d. We therefore studied the intracellular trafficking of human CD1d in Madin-Darby canine kidney (MDCK) and COS cells. CD1d was found in endosomal compartments after its internalization from the plasma membrane. It is therefore possible that CD1d acquires its yet unidentified exogenous ligand in the same compartments as the MHC class II and CD1b molecules. CD1d contains a tyrosine-based sorting signal in its cytoplasmic tail that is necessary for internalization. Furthermore, the cytoplasmic tail of CD1d also contains a signal for basolateral sorting that is, however, different from the internalization signal.