Mechano-chemical processing for the solid-state polymorphic transition of theophylline from Form I to Form II has been investigated. Contrarily to the same transition without mechanical energy, the transition was found to proceed without humidity and completed in about 24 h. The effect of additives on the transition was examined by co-grinding with purine derivatives. Except for uric acid, they delayed the transition to Form II, and the presence of paraxanthine resulted in going through a Form III of theophylline. In conclusion, additive selection has an important role for controlling the polymorphic transition and the appearance of polymorphs by mechano- chemical processing.