Thermal and hydration effects on the mobility of compact and branched organic molecules and a bulky pharmaceutical substance loaded in submonolayer amounts onto mesoporous silica have been elucidated using 1H and 31P solid-state NMR. In all cases, the ambient hydration has a stronger effect than an increase in temperature to 370 K for water-free silica. The effect of hydration depends on the guest and ranges from complete solvation to a silica-water-guest sandwich structure to a silica-guest/silica-water pattern. The mobility of the guests under different conditions has been described. The specific structure of the MCM-41 surface allows one to study very slow surface diffusion, a diffusivity of about 10-15-10-16 m2/s. The data reported are relevant to any nonfunctionalized silica, while the method used is applicable to any phosphor-containing guest on any host.