Two electrochemical oxidation waves assigned to the D-5h isomer of Sc3N@C-80 have been identified, and a 270-mV difference in the first electrochemical oxidation potentials of the I-h and D-5h isomers has been measured. On the basis of this oxidative potential difference, a strategy for isomeric purification involving a selective chemical oxidation of the D-5h isomer is reported. Variable scan cyclic voltammetry of the resultingly pure Sc3N@C-80 I-h isomer shows evidence of a rapid endohedral chemical reaction following the first reduction process.