A widely used artificial aging methodology is thermo-cycling. The ISO TR 11450 standard (1994) recommends 500 cycles in water between 5 and 55 degrees C. Recent literature revealed that more cycles are needed to mimic long-term bonding effectiveness. Furthermore, the artificial aging effect induced by thermo-cycling is not clearly established. Two underlying mechanisms can be advanced: (1) hot water may accelerate hydrolysis and elution of interface components and (2) repetitive contraction/expansion stress can be generated. OBJECTIVES: The purpose of this study was to evaluate the relative contribution of both chemical (hydrolysis and elution of interface components) and mechanical (repetitive contraction/expansion stress) degradation pathways on the thermo-cycling-induced artificial aging of dentin-adhesive interfaces at the bottom of class-I cavities. METHODS: The micro-tensile bond strength (muTBS) of contemporary adhesives (a three-step etch and rinse, a two-step and a one-step self-etch adhesive) bonded to class-I cavity-bottom dentin was determined after 20,000 cycles as well as after 20 days of water storage (control). Restored class-I cavities (repetitive contraction/expansion stress) as well as prepared micro-specimens (diffusion-dependent hydrolysis and elution) were subjected to the thermo-cycling regimen. RESULTS: Thermo-cycling did not enhance chemical or mechanical degradation of the bonds produced by a two-step self-etch and a three-step etch and rinse adhesive to dentin. The one-step self-etch adhesive tested was, however, not able to withstand polymerization shrinkage stress, nor thermo-cycling, when applied in class-I cavities. SIGNIFICANCE: Thermo-cycling results in combined contraction/expansion stress and accelerated chemical degradation. However, the relative contribution of each is strongly dependent on the specific test set-up and the adhesive used.