The morphologic correlates of bond degradation in self-etching primers have not been fully elucidated. We hypothesized that there is no difference between the mechanism of degradation of self-etching primers in vivo and in vitro. Class I cavities prepared in vivo in 24 caries-free human molars were bonded with Clearfil SE Bond or Clearfil Protect Bond, and restored with resin composites. Eight teeth were extracted after 24 hrs, and the rest after 1 yr. The same protocol was repeated in vitro with extracted molars. Degradation of resin-dentin bonds was assessed by microtensile bond testing and TEM of interfaces after tracer immersion. Both in vivo and in vitro bond strengths decreased with time for SE Bond but not for Protect Bond, with more pronounced water treeing observed in the former adhesive under both aging conditions. There is no difference between the mechanism of degradation of self-etch adhesives in vivo or in vitro.