Heat of hydration of theophylline anhydrate to the monohydrate at 298 K was evaluated by three different methods. The values determined by heat of solution with a microcalorimeter and heat of dehydration with a differential scanning calorimeter were -9.34±0.65 and -9.82±0.48 kJ/mol, respectively. The values obtained directly with a heat conduction microcalorimeter under 97.3, 95.4 and 93.7% relative humidities were -9.48±0.49, -9.28±0.63 and -9.37±0.74 kJ/mol, respectively. From thermograms obtained with a microcalorimeter at the isothermal transition of theophylline anhydrate to monohydrate, hydration rates were analyzed by a deconvolution method. Hydration rates were in good agreement with those obtained by the Karl Fischer method. Hydration mechanisms were also analyzed on the basis of solid-state kinetic models and the transition followed a mechanism of random nucleation and two-dimensional growth of nuclei.