Nitrile-modified molecules have proven to be excellent probes of local environments in biomolecules via both vibrational and fluorescence spectroscopy. The utility of the nitrile group as a spectroscopic probe has been expanded here to (15)N NMR spectroscopy by selective (15)N incorporation. The (15)N NMR chemical shift (δ((15)N)) of the (15)N-labeled 5-cyano-2'-deoxyuridine (C(15)NdU, 1a) was found to change from 153.47 to 143.80 ppm in going from THF-d(8) to D(2)O. A 0.81 ppm downfield shift was measured upon formation of a hydrogen-bond-mediated heterodimer between 2,6-diheptanamidopyridine and a silyl ether analogue of 1a in chloroform, and the small intrinsic temperature dependence of δ((15)N) of C(15)NdU was measured as a 0.38 ppm downfield shift from 298 to 338 K. The experiments were complemented with density functional theory calculations exploring the effect of solvation on the (15)N NMR chemical shift.