This article presents a description of the initiation of chemistry in molecular solids by laser excitation under high-pressure conditions. An experimental and theoretical study on the initiation of cyclotrimethylene triamine (RDX) suggests that the initiation process involve electronically excited states. Ab initio calculations on RDX crystals including vacancies and edge dislocations are used to provide an interpretation of the measured RDX initiation properties at pressures up to 5.0 GPa and 2 laser fluences between 1.0 and 10 J/cm(2).