The resin-dentin interface of in vivo specimens restored with the All-Bond 2 system by use of a total-etch wet-bonding technique on vital deep human dentin was investigated by: (a) SEM examination of cryofractured specimens; (b) SEM examination of acid-rinsed, highly polished, embedded specimens; and (c) TEM examination of demineralized ultrathin sections. Ultrastructural features that were pertinent to the formation of an effective clinical seal were characterized. It is suggested that the establishment of an effective seal of the patent dentinal tubules following total etching is accomplished by: (1) the formation of an outer zone of a solid resin plug surrounded by a circumferential cuff of resin-impregnated dentin; and (2) the formation of an inner zone of a hollow resin sheath with resin globules along the internal walls of the tubules, closely adapting to the odontoblast process. The structural appearance and functional implications of these two zones were strikingly similar, with the sealing of exposed dentinal tubules in arrested carious lesions or cervical abfraction lesions. It appeared that there is a common denominator in physiologic isolation defense mechanisms and the total-etch, wet-bonding technique in the All-Bond 2 system in preserving the biological and morphological integrity of the pulpo-dentinal complex.