A commercially available computer-controlled vacuum moisture balance was used for determining moisture sorption isotherms of freeze-dried and spray-dried lamotrigine mesylate drug substance and freeze dried drug product containing mannitol. The presence or absence of desorption hysteresis and the characteristics of the weight-versus-time profile as a sample was exposed to a defined relative humidity ramp were sensitive indicators of moisture-induced crystallization. Combination of the moisture sorption data with polarized light microscopy, differential scanning calorimetry, and X-ray powder diffraction provided qualitative verification of the crystallization with < 50 mg of sample. The normalized water loss during crystallization was used to detect as little as 2% amorphous content in physical mixtures of amorphous and crystalline lamotrigine mesylate. Moisture sorption, water plasticization, and crystallization properties of amorphous forms prepared by spray drying and freeze drying were nearly identical. Cofreeze-drying lamotrigine mesylate with D-mannitol resulted in a mixture of amorphous lamotrigine mesylate with properties similar to those of spray-dried or freeze-dried materials and crystalline D-mannitol. The amount of water needed for crystallization over a time scale observable in the moisture balance was considerably more than the amount needed to lower the glass transition temperature of the sample to the operating temperature of the instrument. This result illustrated the importance of time scale effects in determining critical moisture levels for crystallization from the amorphous state.