The fate of TNF after binding to the surface of L-929 cells was followed by using murine rTNF coupled to colloidal gold as a probe. A time-course study using electron microscopy was performed. Our results confirm previous indications obtained from biochemical studies suggesting that TNF is internalized by this cell type. They further directly show that internalization proceeds through the classical receptor-mediated endocytosis pathway, i.e., via clathrin-coated structures and endosomes before accumulation in secondary lysosomes.