OBJECTIVE To investigate and compare the in vivo and in vitro tensile bond strengths of a 4-META/MMA-TBB adhesive resin (Superbond C&B, C&B-Metabond) to human dentin. METHODS Caries-free teeth present on patients and scheduled for extraction for orthodontic reasons were used. Flat dentin surfaces were prepared and a 4-META/MMA-TBB resin applied. After 10 minutes, the teeth were extracted. Extracted caries-free teeth were also used and treated similarly. Tensile bond strength was evaluated and all specimens were sectioned immediately after bond testing, after polishing the debonded area or after treating the surfaces with HCl acid. RESULTS Data were analyzed statistically, and no significant differences could be determined between third molars and first premolars, and in vivo and in vitro specimens. Further, tensile stress fractured specimens were examined under scanning and transmission electron microscopy. Widths (+/- 5 microns) of hybrid layers and impregnation of adhesive monomers into 10-3 solution demineralized vital human dentin substrates were essentially similar to those observed in extracted samples. The adhesive resin penetrated tubules to form resin tags, unimpeded by intra-tubular fluid under physiologic pressure in intra-orally prepared specimens. A hybrid layer formed on resin tags to seal against microleakage and pulpal attack by bacteria and their by-products. An acid-resistant hybrid layer was also observed in enamel. Finally, hydroxyapatite crystals that were encapsulated by polymerized 4-META/MMA-TBB resin was observed at the bases of resin-reinforced hybrid layers in the human dentin substrates. This observation is consistent with earlier findings and appears to be essential in maintaining durable dentin bonds.