Differences in refractive index between deuterated and normal solvents have been determined using a conventional gel permeation chromatograph equipped with a differential refractometer detector. Three molecular systems have been studied, namely, water–deuterium oxide, acetone–acetone (d6), and tetrahydrofuran–tetrahydrofuran (d8). A plot of the signal intensity versus the concentration of the deuterated solvent in the normal solvent gave a linear relationship for all three systems studied. The effect of deuteration is found to result in a lowering of the refractive index which is at least three orders of magnitude larger than the sensitivity of the differential refractometer. Consequently, for permeation chromatographic studies, the addition of 1% or less of the deuterated solvent in the injection sample would be more than sufficient to produce a peak characteristic of the mobile phase.