In order to understand the mechanisms involved in the hypertrophy of vascularized bone grafts, a series of animal experiments were carried out and 32 clinical cases were studied. A defect in the tibial shaft was created in puppies and the ipsilateral fibula was transferred into the medullary cavity of the tibia with the anterior tibial artery and vein. The same procedure was performed on a control group but without vessel supply. Radiologically, in the vascularized group mild hypertrophy in the fibula was seen at 2 weeks, became marked by 4 weeks, but in no case did the thickening (hypertrophy) of the graft ever exceed the diameter of the recipient tibia. The control group did not show hypertrophy but fracture callus formed in the recipient tibia at both ends of the graft. On histological evaluation no reactive bone formation was evident in the control group but some reactive bone formation was seen in the vascularized group just beneath the periosteum. There was no change in the periosteum itself. In the clinical cases 47% of patients showed hypertrophy. Hypertrophy was noted mainly in the fibulae but rarely in other bones such as ilium or rib. The important factors were age and good vascularity of the grafted bone. During the period of study, weight-bearing was eliminated, so that the effects of mechanical force did not explain hypertrophy. We conclude from these studies that true hypertrophy is an essentially different process from reactive callus which forms normally in response to fracture healing. Vascularized bone grafts show remarkable hypertrophy of the grafted bone, but the exact mechanism is ill defined.(ABSTRACT TRUNCATED AT 250 WORDS)