Purpose: To investigate the interaction of six experimental and commercial bonding systems with dentin in vivo. Materials and Methods: One-Step, Clearfil Liner Bond 2, OptiBond, Permagen with 10% phosphoric acid, Permagen with 35% phosphoric acid, and Prime & Bond were applied in standard Class I occlusal cavities in premolars scheduled for extraction for orthodontic reasons, combined either with a self-cured or with a light-cured resin composite. The teeth were carefully extracted 5 minutes after resin polymerization and fixed in 2.5% glutaraldehyde. After fixation, the specimens were dehydrated, sectioned, and processed for field-emission SEM. Results: Although some systems produced gap-free intact interfaces in specific specimens, all of them showed detachment at the transition between the resin-dentin interdiffusion zone and the fluid resin placed over it. It was apparent that the presence of air-bubbles and/or thick layers of polymerized-filled fluid resin resulted in less frequent separation areas at the resin-dentin interface, providing support for the concept of the elastic cavity wall. It was also confirmed that some dentin adhesive systems do not form a thick layer over the dentin, otherwise the resin composite would not have penetrated the dentin tubules