The intracellular fates of soluble and liposomal antigens in human macrophages and dendritic cells are not well defined. Previous studies using murine macrophages have demonstrated that liposomal antigens can enter the MHC class I pathway. The Golgi complex is a major organelle in this pathway. Phagocytosis of the antigens is followed by translocation of antigen-derived peptides to the trans-Golgi where they can complex with MHC class I molecules. In contrast, soluble antigens are normally processed through the MHC class II pathway. Therefore, in the present study, ovalbumin and a synthetic Ebola peptide were used either in a soluble form or encapsulated in liposomes to investigate the intracellular trafficking and localization of these antigens to the Golgi complex in human macrophages and dendritic cells. While liposome-encapsulated antigens were transported to the trans-Golgi region in 59-78% of macrophages, soluble antigens remained diffuse throughout the cytoplasm with only 3-11% of the macrophages exhibiting trans-Golgi localization. The majority of dendritic cells localized both soluble (Ebola, 75%; ovalbumin, 84%) and liposomal antigens (58% and 65%), and irradiated Ebola virus to the trans-Golgi. These studies demonstrate that the intracellular fate of soluble and liposomal antigens can differ depending upon the antigen-presenting cell.