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 N-15 NMR spectroscopy by selective N-15 incorporation. The 15N NMR chemical shift (delta N-15) of the N-15-labeled 5-cyano-2'-deoxyuridine ((CNdU)-Nd-15, 1a) was found to change from 153.47 to 143.80 ppm in going from THF-d(8) to D2O. 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 delta N-15 of (CNdU)-Nd-15 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 N-15 NMR chemical shift.