The in vivo behavior and tissue reaction to tetrahedral amorphous carbon (ta-C) has been evaluated for periods of up to 6 months in SV129 mice. Two sample types were tested--silicon die coated with ta-C (n = 53) and micromachined particles (n = 40). The coated samples were compared to uncoated silicon die (n = 22). Die samples were implanted subcutaneously, and tissue reaction and capsule formation were evaluated at various time points. Micromachined particles of 1, 3, 10, and 30 microm were injected adjacent to the sciatic nerve, and tissue samples were examined histologically at various time points (4 days-6 months). Tissue reaction to ta-C was mild and was localized to the area of the injection or implantation. Samples with a higher ratio of 3-fold bonding appeared to shed material during the experiments; this was not observed on samples with a higher level of 4-fold bonding, nor on uncoated silicon die. The results strongly suggest that films with greater 4-fold bonding character (more diamond-like) are more resistant to in vivo fragmentation than films with higher 3-fold character (more graphitic).