Abstract A histological and histochemical evaluation was conducted in rabbit to study the presence of multinucleated giant cells (MGCs) at the interface with machined, sandblasted and plasma-sprayed titanium implants. No MGCs were observed, at any of the experimental times, around machined and sandblasted titanium surfaces. MGCs were, on the contrary, present at the interface with titanium plasma-sprayed implants at two weeks and at two months. At two weeks these cells were numerous, and in some areas, particularly around the spires, tended to line almost all the implant perimeter surface. MGCs were present in large numbers where bone was present at the interface, while, on the contrary, where there was no newly formed bone, they tended to be fewer in number and smaller in diameter. At four and eight weeks these cells tended to decrease in number. The histochemical staining for acid phosphatase (ACP) and alkaline phosphatase (ALP) showed that MGCs were negative to ACP, while many ALP-positive osteoblasts, actively secreting osteoid matrix, were in close and tight contact with the MGCs. In no case was an inflammatory infiltrate present in connection with the MGCs. The precise nature of MGCs is still not clear, but our histological and histochemical results could point to a priming effect on the activity of the osteoblasts in a similar way to the supposed role of the osteoclasts.