In situ time-of-flight secondary ion mass spectrometry, infrared spectroscopy, and X-ray photoelectron spectroscopy measurements have been used to characterize the interfacial chemistry that occurs upon physical vapor deposition of Ti and Ca atoms onto a -OCH(3) terminated alkanethiolate self-assembled monolayer (SAM) on Au{111}. While the final result for both metals is near-exhaustive degradation of the methoxy terminal group and partial degradation of the alkyl chains to inorganic products such as carbides, hydrides, and oxides, the reaction mechanisms differ significantly. Titanium reacts in parallel with the -OCH(3) and -CH(2)- units, extensively degrading the latter until a metallic overlayer forms preventing further degradation. At this point, there is a cessation of the Ti-SAM reactions. In contrast, Ca is initially consumed by the -OCH(3) terminal group via a reaction mechanism involving two -OCH(3) groups; subsequent depositions lead to alkyl chain degradation, but at a rate slower than that for Ti deposition. These results demonstrate the subtle differences in chemistry that can arise in the vapor deposition of reactive metals, and have important implications for the behavior of electrical interfaces in organic and molecular devices made with Ti or Ca top contacts.