Orally administered dosage forms receive a destructive force in the gastrointestinal (GI) tract due to peristalsis. In this study, the destructive force was measured with a 'destructive force-dependent release system' (DDRS). DDRS is a press-coated tablet with an extremely brittle outer layer composed of highly hydrophobic Teflon(R) powder, which is molded with a weak compression force. Teflon(R) powder forms a porous but water-impermeable layer around the core tablet. A marker drug contained in the core tablet is released only when the tablet receives a force larger than its pre-determined crushing strength. A comparison of the physiological conditions in the GI tract of dogs with those of humans, including the destructive force against tablets in the stomach, helps us to understand their difference in bioavailability of oral dosage forms. With DDRS, it is possible to evaluate the destructive force of both human and dog stomach using the same method. Therefore, the destructive force data from human and dog can be directly compared. The destructive force in the dog stomach was evaluated to be 3.2 N, which was considerably stronger than that of humans.