A methyl Transverse Relaxation Optimized Spectroscopy (methyl-TROSY) based, multiple quantum (MQ) 13 C Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion NMR experiment is described. The experiment is derived from the previously developed MQ 13 C- 1 H CPMG scheme (Korzhnev in J Am Chem Soc 126: 3964-73, 2004) supplemented with a CPMG train of refocusing 1 H pulses applied with constant frequency and synchronized with the 13 C CPMG pulse train. The optimal 1 H 'decoupling' scheme that minimizes the amount of fast-relaxing methyl MQ magnetization present during CPMG intervals, makes use of an XY-4 phase cycling of the refocusing composite 1 H pulses. For small-to-medium sized proteins, the MQ 13 C CPMG experiment has the advantage over its single quantum (SQ) 13 C counterpart of significantly reducing intrinsic, exchange-free relaxation rates of methyl coherences. For high molecular weight proteins, the MQ 13 C CPMG experiment eliminates complications in the interpretation of MQ 13 C- 1 H CPMG relaxation dispersion profiles arising from contributions to exchange from differences in methyl 1 H chemical shifts between ground and excited states. The MQ 13 C CPMG experiment is tested on two protein systems: (1) a triple mutant of the Fyn SH3 domain that interconverts slowly on the chemical shift time scale between the major folded state and an excited state folding intermediate; and (2) the 82-kDa enzyme Malate Synthase G (MSG), where chemical exchange at individual Ile δ1 methyl positions occurs on a much faster time-scale.