A new inclusion compound consisting of a guanidinium 1,3,5-tri(4-sulfophenyl)benzene (G(3)TSPHB) host framework containing isophorone guests that surround isolated and seemingly inaccessible pockets was amenable to guest exchange with hexafluorobenzene (HFB) through a single crystal-single crystal transformation (SCSCT). Single-crystal X-ray diffraction of intermediate transformation states, from the parent compound G(3)TSPHB center dot(isophorone)(3.7)center dot(methanol)(5.4) to the final state G(3)TSPHB center dot(isophorone)(3.1)center dot(HFB)(2)center dot(methanol)(2), indicated a crystal symmetry change from monoclinic to hexagonal prior to full incorporation of HFB. Optical microscopy during the SCSCT revealed the formation of lamellae, which expanded and then coalesced into a single crystal when the phase transformation was complete. In situ Raman microscopy revealed changes in the orientation of isophorone guests during the transformation that suggested a pathway for HFB entry into the host cavities. The SCSCT occurs more rapidly than expected on the basis of simple diffusion, consistent with facilitated transport along the lamellae interfaces and a reduction in the length scale for guest exchange.