The transporter associated with antigen processing (TAP) delivers cytosolic peptides into the endoplasmic reticulum (ER) where they bind to nascent class I histocompatibility molecules. Class I-peptide complexes are then displayed at the cell surface for recognition by cytotoxic T lymphocytes. Immunoprecipitation of either TAP or class I molecules revealed an association between the transporter and diverse class I products. TAP bound preferentially to heterodimers of the class I heavy chain and beta(2)-microglobulin, and the complex subsequently dissociated in parallel with transport of class I molecules from the ER to the Golgi apparatus. The TAP-class I complexes could also be dissociated in vitro by the addition of class I-binding peptides. The association of class I molecules with TAP likely promotes efficient capture of peptides before their exposure to the lumen of the ER.