The reactivity of metals vapor deposited onto organic monolayers has historically been correlated to the metal/terminal organic group chemistry. Here we demonstrate that the chemical composition of the substrate unexpectedly plays a significant role as well. In particular, the reactivity of evaporated titanium toward a cadmium stearate Langmuir-Blodgett (LB) film was found to depend on the substrate upon which the LB film was deposited. Infrared spectra taken in a modified ATR (Kretschmann) geometry with a thin Au substrate showed large changes in peak shape, peak position, and peak width in the C-H stretching region, indicating titanium penetration into the LB film and decomposition of the original well-packed monolayer structure. LB monolayers formed on a platinum oxide (PtOx) surface showed remarkably small changes after Ti deposition, indicating only a slight increase in disorder and no significant metal penetration into the film. Films on SiO2 substrates showed reactivity between that of Au and PtOx. These differences in reactivity can be correlated primarily with the amount of available oxygen associated with each substrate, including surface oxide layers and water incorporated within the LB film.