Amantadine and related compounds stabilized the structure of purified pig brain clathrin coated vesicles (CCV) at biologically relevant concentrations. Incubation of purified CCV for 30 min at 25°C or 37°C caused the release clathrin, as determined by a centrifugation assay, and a reduction in the number of coated vesicles, by electron microscopy. Amantadine (10 mM), tromantadine (1 mM), amidine D295 (cyclohexylcarboximidamide-(N-benzyl)hydrochloride) (10 mM), chloroquin (0.1 mM) and monodansyleadaverine (10 mM) significantly reduced the extent of dissociation.