The effect of isotopic substitution on the natural frequencies of vibrational-rotational transitions in diatomic and triatomic molecules is discussed in order to show how new infrared maser frequencies can be obtained which differ significantly from the original. The magnitude of this effect, in which the ratio of the original frequency to the isotopically shifted frequency may be as great as 1.4 in one case considered, is to be constrasted with the corresponding isotope effect on the frequency of electronic transitions in atoms, where the shift in frequency thus obtained is extremely small, typically amounting to one part in 104. The calculated effect of the isotope shift on the frequencies of two known diatomic molecular infrared masers is given for selected isotopes. The results of an experiment in which 018was substituted for 016in the CO2infrared maser are given as an interesting example of the isotope effect on a triatomic molecule. It is found that the dominant 10.6 μ maser transition in C12O216is shifted to 9.4 μ while the 9.5 μ transition is shifted to 10.4 μ as a result of double substitution of O18for O16in the CO2molecule. In conclusion, several advantages for spectroscopy and infrared technology are mentioned as resulting from the availability of new coherent infrared sources.