The supramolecular host assembly [Ga4L6](12-) [1; L = 1,5-bis(2,3-dihydroxybenzamido)naphthalene] contains a flexible, hydrophobic interior cavity that can encapsulate cationic guest molecules and catalyze a variety of chemical transformations. The Ar-CH2 bond rotational barrier for encapsulated ortho-substituted benzyl phosphonium guest molecules is sensitive to the size and shape of the host interior space. Here we examine how changes in bulk solvent (water, methanol, or DMF) or applied pressure (up to 150 MPa) affect the rotational dynamics of encapsulated benzyl phosphonium guests, as a way to probe changes in host cavity size or flexibility. When host 1 is dissolved in organic solvents with large solvent internal pressures (partial derivative U/partial derivative V)(T), we find that the free energy barrier to Ar-CH2 bond rotation increases by 1-2 kcal/naol, compared with that in aqueous solution. Likewise, when external pressure is applied to the host-guest complex in solution, the bond rotational rates for the encapsulated guests decrease. The magnitude of these rate changes and the volumes of activation obtained using either solvent internal pressure or applied external pressure are very similar. NOE distance measurements reveal shorter average host-guest distances (similar to 0.3 angstrom) in organic versus aqueous solution. These experiments demonstrate that increasing solvent internal pressure or applied external pressure reduces the host cavity size or flexibility, resulting in more restricted motions for encapsulated guest molecules. Changing bulk solvent or external pressure might therefore be used to tune the physical properties or reactivity of guest molecules encapsulated in a flexible supramolecular host.