Studies of the mass-independent effect on oxygen isotope fractionation (MIF) are summarized, focusing on the MIF in ozone formation in the laboratory, a similar effect being found in the atmosphere. (As used here the MIF for O isotopomers means that the usual three-isotope plot has a slope of about unity instead of the conventional 0.52.) The marked difference of results obtained with systems when there is extensive isotopic exchange (“scrambled”) and experimental conditions where isotopic exchange is minimized (“unscrambled”) is also discussed. Ratios of rate constants can be measured only in the latter and show large isotope effects. These large isotope effects were shown to cancel exactly when there is extensive isotopic exchange, and one then obtains instead an MIF for ozone. We also consider a possible role of the chaperon versus energy transfer mechanisms for ozone formation in influencing the temperature dependence of the MIF. MIF in other systems are noted. Separately we consider the CO+OH→CO_2 reaction, an isotopically anomalous reaction. It has sometimes been called “mass-independent” but has no O atom symmetry for the HOCO∗ intermediate and so no MIF in the above sense (ca. unit slope) would be expected on theoretical grounds.