Recent histological studies have demonstrated that the substitution of silicate ions into hydroxyapatite (HA) significantly increases the rate of bone apposition to HA implants. The enhanced bioactivity of silicon-substituted HA (Si-HA) over pure HA has been attributed to the effect of silicate ions in accelerating dissolution. In the present study, high-resolution transmission electron microscopy (HR-TEM) was employed to compare dissolution of HA and Si-HA in an acellular simulated body fluid (SBF) to dissolution in an in vivo model. HR-TEM observations confirmed a difference in morphology of apatite precipitates in vivo and in SBF: apatite deposits were platelike in vivo and nodular in SBF. Compositional mapping suggested that preferential dissolution of silicon from the implant promotes the nucleation of carbonate apatite around the implant. The in vivo findings illustrated an absence of dissolution at the bone-HA or Si-HA interface, whereas dissolution was extensive from within the implant. The amount of dissolution in acellular SBF was similar to dissolution from within the implant, although the site at which the dissolution nucleates was different: dissolution predominates at the crystallite surfaces in SBF, whereas grain boundary dissolution predominates in vivo. These findings suggest that proteins in the in vivo milieu modify the processes of dissolution from the implant.