The diffusion of methyl ethyl ketone (MEK) in two vinyl alcohol/vinyl butyral (VA/VBu) copolymers (11- and 19-wt. % VA) was studied at low vapor activities using Fourier transform infrared-attenuated total reflectance (FTIR-ATR) spectroscopy. MEK has the ability to interact through hydrogen bonding to sites in the polymer and was chosen to study the effect of penetrant–polymer solvation on molecular diffusion. The assumption of local equilibrium was verified by examining the time-evolved concentrations of hydrogen-bound and free MEK determined from the carbonyl (C = O) stretching bands. A mathematical model that accounted explicitly for solvation during the diffusion process was developed. Solvation hindered the diffusion of MEK in the VA/VBu copolymer by factors of 2.0 (11-wt. % VA) and 2.6 (19-wt. % VA). After separating solvation from diffusion, true diffusion coefficients of MEK were compared to those of methylene chloride (CH2 Cl2 ), a noninteracting penetrant of similar size to MEK. Within experimental error, true diffusion coefficients for MEK were the same as those for CH2 C12 over the concentration range studied.