Exogenous proteins are generally not presented through the major histocompatibility complex (MHC) class I pathway, yet several recent studies show that particle-associated antigens induce a CD8+ T-cell response. Therefore, a pathway must exist in vivo for the presentation of exogenous antigens on class I molecules. In the present study, we investigated the intracellular fate of liposome-encapsulated Texas Red (TR)-conjugated protein in cultured bone marrow-derived macrophages (BMs). After phagocytosis of liposomes, the fluorescent liposomal protein, initially associated with the liposomal lipids in phagosomes, later entered the cytoplasm, and the processed protein was subsequently visualized in the trans-Golgi as a fluorescent peptide. Experiments performed with BMs from transporter associated with antigen processing (TAP1) knock-out mice demonstrated that the translocation of peptides into the trans-Golgi area was dependent upon TAP1 protein. We conclude that delivery of liposomal proteins or peptides to the cytoplasm of phagocytes and subsequent transport of peptides to the Golgi via the classical MHC class I pathway involving TAP proteins might explain the known propensity of liposomal antigens to induce cytotoxic T-lymphocytes (CTLs).