Objective To compare the endocytic routes of exogenous antigen between murine dendritic cells (DCs) and macrophages (M phis). Methods Murine bone marrow-derived DCs and peritoneal M phis were pulsed with horseradish peroxidase (HRP)-5 nm colloidal gold for 10 minutes, then grouped and chased for 0 - 120 minutes in culture medium. Intracellular distribution of 5 nm colloidal gold was explored by means of the cellular enzymatic-chemistry of acid phosphatase and MHC II immuno-cytochemistry under electron microscope. Results After 10 minutes of pulse with HRP-5 nm colloidal gold and 30 minutes of chase, most HRP-5 nm gold particles internalized by DCs entered into MHC class II. compartments (M II Cs), and a small portion entered into acid phosphatase-positive lysosomes. In contract to DCs, most M phis lysosomes were accessed by HRP-5 nm gold particles, and a small portion of HRP-5 nm gold particles entered into M II Cs. After 60 minutes of chase, 5 nm gold particles could hardly be seen within M phis, whereas most 5 nm gold particles were still retained in DCs. Conclusions The endocytic route of exogenous antigen in DCs seems to be different from that in M phis. Antigens taken by M phis mainly enter into lysosomes within 30 minutes. In the case of DCs, most internalized antigens enter into M II Cs, which may be related to their unique antigen-presenting function. In addition, M phis seem to have more powerful capacity to scavenge exogenous antigen than DCs.