We present a gradient selected and doubly sensitivity-enhanced DE-MQ-(H)CC(m)H(m)-TOCSY experiment for the sequence-specific assignment of methyl resonances in (13)C,(15)N labeled proteins. The proposed experiment provides improved sensitivity and artifact suppression relative to the phase-cycled experiments. One part of the (13)Cchemical shift evolution takes place under heteronuclear multiple quantum coherence, whereas the other part occurs under (13)C single quantum coherence in a semi-constant time fashion. The feasibility of the experiment was assessed using (15)N,(13)C labeled Mus musculus coactosin (16 kDa), having a rotational correlation time of 14.5 ns at 15 degrees C in D(2)O. A 16-h experiment on 600 MHz (1)H yielded good quality data and enabled the assignment of 70 out of 72 methyl groups in coactosin. As well as being an improved approach for methyl resonance assignment, this experiment can also be highly valuable for the rapid assignment of methyl resonances in SAR by NMR studies.