The effect of overloading and underloading on tissue ingrowth into the porous-coated titanium segmental prosthesis was studied in a canine femoral model. The prosthesis has modular components that are connected by a conical coupling joint. One of the dog's hind legs was immobilized and suspended for three weeks using an external fixator to minimize loading and prevent weight-bearing, while the contralateral leg was allowed to bear weight freely, simulating an overloading situation. Five dogs reached the final study period of twelve weeks without complication. There were no significant differences between the non-weight-bearing and weight-bearing sides on radiographic assessments. However, the immobilized side had significantly higher stem-push-out strength and energy to failure. Bone ingrowth was variable, and a fibrous layer was commonly demonstrated at the prosthetic stem-bone interface. The orientation of the fibrous tissue was more organized, in a penetrating pattern, on the immobilized side. The mean concentration of titanium was insignificant in all tissue examined. Reduced implant loading for the porous-coated segmental bone prosthesis during the initial period of implantation was found to be beneficial as compared with an overloading situation in achieving intramedullary fixation.