A new NMR experiment is described for recording NOEs from Val and Ile methyl groups in N-15,C-13- labeled or methyl-protonated, N-15,C-13,H-2-labeled proteins that offers far superior resolution than conventional 3D C-13-edited NOESY data sets. Resolution is achieved by recording both the C-beta and C-gamma (Val) or C-gamma 2 (Ile) chemical shifts as well as the chemical shift of the destination proton, and a strategy is introduced for refocusing homonuclear carbon couplings during the constant-time evolution of C-beta carbon magnetization. The utility of the method is demonstrated with applications on a 160-residue fully protonated N-15,C-13-labeled, dNumb PTB domain-peptide complex and a methyl protonated, highly deuterated N-15,C-13-labeled complex of maltose binding protein and beta-cyclodextrin (42 kDa).