The TAP1/2 complex translocates peptides from the cytosol into the endoplasmic reticulum. In the rat, TAP polymorphism affects the pool of peptides presented by major histocompatibility complex class I molecules, whereas in mouse and humans the functional consequences of observed structural polymorphism have not yet been determined. Peptide binding to TAP precedes ATP binding, and ATP hydrolysis is required to release and translocate peptides. Cytosolic peptides entering the class I pathway via the TAP complex may differ significantly in size and sequence. Not all peptides that are able to bind to TAP can be translocated into the endoplasmic reticulum, and TAP-binding affinity does not directly correlate with antigenicity of the peptide. Most translocated peptides are released from the endoplasmic reticulum by an incompletely defined ATP-dependent mechanism. TAP interaction with class I molecules stimulates peptide binding and transport by TAP and may also facilitate efficient loading of class I with peptides. Pathogenic microorganisms, such as herpes simplex virus, may encode inhibitors of TAP-mediated peptide transport in order to evade immune surveillance.