The rate of fracture-healing is accelerated and abundant callus develops in patients who have a head injury and fractures. The mechanism underlying this is unclear. We studied the possibility that increased circulating growth factors or circulating factors that stimulate local release of growth factors mediate the increased osteogenesis. Samples of serum were obtained from thirty-two subjects: patients who had a head injury alone, those who had a head injury and fractures of the lower extremities, those who had only fractures, and control subjects who had neither a head injury nor a fracture. Severe head injury was defined as that producing coma of at least three days' duration. Growth-factor activity was determined by assessing the effect of serum on the incorporation of [3H]thymidine and on cell counts in primary cultures of osteoblastic cells from the calvaria of fetal rats. Samples of serum from the two groups of patients who had a head injury had higher mitogenic activity and produced a greater increase in the number of cells than did the samples from the other two groups. The mean levels of activity were not statistically different between the first two groups or between the patients who had fractures only and the control subjects. Dilution studies showed that increased mitogenic activity in the serum from the patients who had a head injury was dose-dependent. In three patients in whom it was studied, the mitogenic activity peaked approximately thirty-seven days after the head injury was sustained.