Purpose: To demonstrate the ability of thermally stimulated current (TSC), normally used to study amorphous systems, in detecting weak solid-solid transitions in crystalline pharmaceutical compound. Methods: Polymorphs of a new chemical entity, LAU254, were generated and characterized using conventional and hot plate X-ray diffraction, DSC and TSC. Equilibration of 50:50 mixtures of the different polymorphs and solubility studies were conducted in aqueous and organic solvent at 25 and 50degreesC and then analyzed by X-ray and DSC. Results: Four crystalline forms (A-D) were isolated. Form B showed one single endotherm at 180degreesC while the other forms showed lower melting endotherms, a crystallization exotherm and eventually a final melting endotherm corresponding to that of form B (180degreesC). The heat of fusion of form B was the highest. In contrast, solubility as well as mixture equilibration studies resulted in all forms converting to form A. TSC analysis revealed a well-defined reproducible peak with a maximum at similar to130degreesC which was suspected to be a solid-solid transition. This was confirmed by hot plate X-ray diffraction where careful probing around 120-130degreesC revealed three different forms; form A (the initial form), a second form that appears above 150degreesC, melts, crystallizes and produces form B. Careful inspection of larger sample sizes in DSC showed a small endotherm at similar to130degreesC. Conclusions: TSC, normally used to study amorphous systems, proved to be useful in detecting weak solid-solid transitions in crystalline pharmaceuticals, an application that has never been explored or reported previously. This resulted in identifying a form, obtainable only at temperatures above the transition temperature (related enantiotropically to the form that is most stable at ambient temperatures) and in reconciling the DSC and solubility data. TSC can be very useful in detecting and probing those transitions that occur in the solid state due to subtle dipolar motion and are not associated with large changes in global motion and heat capacity that is needed for detection by DSC and therefore can be complementary to DSC in obtaining a more complete assessment of the polymorphism behavior of crystalline solids. (C) 2004 Elsevier B.V. All rights reserved.