A newly developed system of microscopic Fourier-transform infrared spectroscopy combined with differential scanning calorimetry was used to determine simultaneously the thermoresponsive IR spectral change of a physical mixture or a cast film of theophylline and Eudragit L-100 by means of a three-dimensional plot. The results indicated that this newly developed system was quick, simple and useful for determining the glass transition of the physical mixture or cast film. Because of the hydrogen bonding occurring in the cast film, the glass transition temperature of the cast film was higher than that of the physical mixture or Eudragit L-100 alone. An interaction between theophylline and Eudragit L-100 was also found in the physical mixture during DSC heating. Moreover, we found that the formation of an acid anhydride by a crosslinking process also took place in Eudragit L-100 polymer at elevated temperature.