The H 2 16 O/H 2 18 O solvent-induced isotope shifts ( 18 O SIIS) of the 19 F NMR signals of a number of fluorine compounds have been measured. These isotope shifts are observed to be upfield, downfield, or zero, depending on the specific compound and the precise solution conditions. At 25Β°C and with an 18 O enrichment of 86%, the 18 O SIIS of several fluorinated amino acids were in the range of 0.0014 -0.0018 ppm downfield. 5-Fluorouridine displays a significantly wider range of 18 O SIIS values. A 5-fluorouridine-labeled 16-mer RNA also displayed observable 18 O SIIS values, but the characteristics of these were significantly modified from those of free 5-fluorouridine. The experimental observations are consistent with the 18 O SIIS being composed of upfield and downfield components, with the relative contributions of these determining the size and direction of the overall isotope shift. This is discussed in terms of a combination of van der Waals interactions between the fluorine atom and the solvent, electrical and hydrogen bonding effects, and the perturbations to these due to 18 O substitution in the solvent water. This isotope effect promises to be a highly useful tool in a range of 19 F NMR studies.