Three structural motifs in the invariant chain (li) control the intracellular transport of class II major histocompatibility complex molecules. An endo-plasmic reticulum retention signal in the full-length li suggests a role for li in the α–β heterodimer assembly. Another signal motif directs a truncated li, alone or associated with individual class II chains, to a degradation compartment by a pathway circumventing the Golgi. When this truncated li binds α–β dimers, a third signal dominates, directing the complex by way of the Golgi to vesicles in the cell periphery, which may represent a subcompartment of recycling endosomes.