Deuterium labeling has been used to study the processes occurring during the conversion of methanol to methyl formate over copper catalysts at 180-210 °C and pressures of 0.3 to 1 atm. Deuterium substitution has a dramatic effect on rate, which decreases in the ratio 8:4:2:1 in the series CH3OH, CH3OD, CD3OH, CD3OD. This can be interpreted as the product of a primary kinetic isotope effect of four for replacement of CH3 by CD3 and a separate thermodynamic isotope effect of two on the concentration of a surface methoxy intermediate when OH is replaced by OD. The isotope effect provides strong support for a mechanism in which the slow step is the conversion of the methoxy group to formaldehyde. Reversibility of the conversion of methanol to methoxy is reflected by hydroxyl group exchange with D2 at a rate much in excess of methyl formate production. H2/HD/D2 equilibration rates are still faster even though methanol coverages are high. The product distribution from CD3OD CH3OH mixtures shows that methyl formate formation involves transfer of an H or a D with a discrimination isotope effect of two. This rules out coupling by a methoxy plus CHO step but leaves unresolved the possibility that the formate is produced by a hemiacetal intermediate or by formaldehyde dimerization. This lack of resolution results from isotopic scrambling caused by concurrent transesterification reactions as demonstrated using CD3OH CH3OCHO mixtures.