In this study we tested the effect of locally applied transforming growth factor-beta1 (TGF-beta1) on distraction osteogenesis in rabbits. A total of 61 rabbits were studied. Seven days after tibial osteotomy, distraction was started at a rate of 0.25 mm/12 h for 3 weeks. Starting with distraction, TGF-beta1 was applied in four different dosages (0, 10, 20, and 40 ng/day) at the site of osteotomy through a catheter connected to a subcutaneously implanted miniosmotic pump. Rabbits were killed at the end of the distraction period or 3 weeks later, and histological, densitometric, and biomechanical parameters were assessed. TGF-beta1 treatment had no detectable effect on bone mineral density or histologically determined bone volume in the distraction gap but it increased the amount of fibrous tissue in the callus region. Load to failure in uniaxial tension tended to be lower in TGF-beta1-treated animals. In conclusion, TGF-beta1 treatment during distraction osteogenesis did not have a beneficial effect in this model.