A periosteal activation agent (PAA) known to activate the cambium layer of the resting periosteum was applied to the femurs of rabbits for three cases of interest: (1) its effect on the healing of a circular defect in the femur, (2) its effect on bone ingrowth into a porous implant, and (3) its effect on formation of bone along the endosteal surface of the femur. In the first two cases, PAA was applied to the periosteal surface of the diaphyses of the femurs seven days after surgery at an optimal dosage of 400 mg per kg of body weight. In the empty defect series, two holes, 4 mm in diameter, were drilled through one cortex of each femur. In the implant series, two cylindrical porous implants of high density polyethylene (average pore size of 127 (mu)m and 4 mm in diameter) were implanted in one cortex of each femur. In the endosteal activation series, PAA was applied along the endosteal surface of the femurs at a dosage of 100 mg per kg of body weight (a level chosen to assure rabbit survival) through a hole bored through the trochanter fosse. The contralateral femurs served as controls in all cases;The endosteal activation series showed that PAA enhanced the natural periosteal callus formation elicited by the surgical trauma at 1 (p < .05), 3, 5 (p < .05), 7, 10 (p < .05), and 14 days, but it did not show any enhanced healing of the defect. The implant series also showed enhanced callus formation at 1 (p < .05), 3, 7, 10, and 14 days after application of PAA, but it failed to show any enhanced bone ingrowth into the interstices of the implant. The results of the endosteal activation series were inconclusive. In certain cases, larger amounts of new bone were observed; however, there was great rabbit-to-rabbit variability in the response. Possible reasons for this include the difficulty of administering the PAA to a local endosteal region of interest without causing excessive trauma to the general area of the medullary canal.