The amorphous content of model drugs was evaluated by isotherm microcalorimetry. Two model drugs were employed; lactose as a hydrophilic one and erythromycin as a hydrophobic one. When amorphous lactose was loaded in a sample cell with a water vial, a sharp exothermic peak due to the crystallization was observed. When a mixture of the amorphous and the crystalline forms was loaded, the peak area of the exothermic heat ยฏow was proportional to the amorphous content. Quantiยฎcation could be done with much higher accuracy than by the X-ray powder diffraction method reported in earlier literature. When erythromycin was used as a model drug, the crystallization was not completed by water but by organic solvents, which can dissolve erythromycin. The most adequate solvent for erythromycin was acetonitrile, of which the suitability was elucidated in terms of solubility and vapor pressure. This is the ยฎrst report in which the role of the vapor pressure on crystallization behavior is discussed. The time needed to obtain the crystallization peak was controlled by mixing acetonitrile with water. The strategy to obtain the crystallization peak by microcalorimetry, which enables quantiยฎcation of the amorphous content with high accuracy, is discussed.