Isotopic (delta(17)O and delta(18)O) measurements of stratospheric and mesospheric carbon dioxide (CO2) and oxygen (O-2), along with trace species concentrations (N2O, CO, and CO2), were made in samples collected from a rocket-borne cryogenic whole air sampler. A large mass-independent isotopic anomaly was observed in CO2, which may in part derive from photochemical coupling to ozone (O-3). The data also require an additional isotopic fractionation process, which is presently unidentified. Mesospheric O-2 isotope ratios differed from those in the troposphere and stratosphere. The cause of this isotopic variation in O-2 is presently unknown. The inability to account for these observations represents a fundamental gap in the understanding of the O-2 chemistry in the stratosphere and mesosphere.