An H/D-exchange reaction involving the methyl group of acetonitrile is observed in the small anionic water cluster OH-(CD3CN)(H2O)(2). In this cluster, a randomization of H and D atoms takes place, and in subsequent collisions with CD3CN, the potentially partially deuterated acetonitrile is replaced by the fully deuterated species. In sequential collisions, fully deuterated clusters OD-(CD3CN)(D2O)(2) are obtained as final products. The H/D-exchange does not occur in OH-(CD3CN)(H2O)(3) or larger clusters. Density functional calculations show that in these larger species, the OH- no longer directly attacks the methyl group, and the barriers for H/D-exchange become higher than those for ligand loss reaction channels. This is a very subtle influence of solvation on an H/D-exchange reaction in the gas phase, where a relatively acidic methyl group encounters a strongly basic reaction partner.