Purpose: To examine the effects of collagenase and esterase activity on the microtensile bond strength and nanoleakage at the resin-dentin interfaces of two adhesive systems: a total-etch adhesive (Single Bond 2: SB) and a self-etch adhesive (Clearfil SE Bond: SE). Methods: Resin composites were bonded to the occlusal dentin surfaces of extracted human premolars with either SB or SE. The bonded teeth were sectioned into beams and assigned to one of four storage conditions: phosphate buffer solution (24 hours), phosphate buffer solution (4 weeks), collagenase solution (4 weeks), or esterase solution (4 weeks). Microtensile bond strength was evaluated and analyzed by two-way ANOVA. Failure mode was analyzed under SEM, and nanoleakage was examined with TEM. Results: The bond strength of SE was superior to that of SB after 4-week storage in three aqueous solutions. Collagenase and esterase solutions did not decrease the bond strength of SB any more than the phosphate buffer solution (P> 0.05). In regard to SE, the bond strength after 4-week storage in collagenase solution was lower than in the phosphate buffer solution (P< 0.05). TEM images revealed increasing tendency of nanoleakage in the bonded interfaces after storage in collagenase and esterase solutions.