Titanium and its alloys are widely used as implant materials for dental and orthopaedic applications. To improve their wear and corrosion resistance, several surface modifications that give rise to an outer ceramic layer of rutile have been developed. It is expected that after a long period of functional loading, rutile debris will arise from these modified surfaces. We have compared the in vitro biocompatibility of subcytotoxic doses of rutile and titanium particles of phagocytosable size in primary cultures of human osteoblasts. Particles were visualized using a spectral confocal microscope by reflection. Both types of particles aggregated in the culture media and were efficiently internalized by osteoblasts as agglomerates. Treatment of isolated cultures of osteoblasts with rutile particles stimulated the release of IL-6, PGE2, and GM-CSF to a lesser extent than titanium. The influence of macrophages on the particle-induced stimulation of those local factors was analyzed by coculturing TPA-differentiated THP-1 cells with osteoblasts. Under these conditions, levels of IL-6 and PGE2 after treatment of cocultured osteoblasts with rutile particles were lower than after exposure to titanium. These results indicate that rutile debris shows a lower bioreactivity than titanium when tested in cultures of human osteoblasts and support the improved biocompatibility of titanium-based implants modified to create an outer layer of rutile on their surfaces.