The development of transplant arteriosclerosis (TA) is a major limiting factor for long time survival of transplanted organs. The mechanisms remain unknown but undiagnosed rejections eliciting release of growth factors are thought to be involved in accelerating myointimal proliferation. We hypothesized that IGF-I may be a crucial growth factor in this process. Thus, we studied the effect of IGF-I on the acceleration of rat aortic TA following orthotopic allograft in vivo. We first evaluated the feasibility of IGF-I incorporation into the arterial wall after a short exposure period ex vivo. Abdominal rat aortas (AAo) of the donor strain, Brown Norway (BN, n = 3), were harvested and placed in DMEM at 37 C with 10 or 100 ng/ml of 1 2 5 I-IGF-I for up to 120 minutes. Fig. 1 demonstrates a time dependent incorporation of IGF-I at 100 ng/ml but not at 10 ng/ml. AAo from the donor rats (BN) were placed in 0, 200, or 500 ng/ml of IGF-I solution for 30 minutes and transplanted into histoincompatible recipient rats (Lewis). Tritiated thymidine incorporation of the vascular wall was determined at 7 days (n = 4). The degree of intimal thickening was examined at 14 days (n = 7) using computerized morphometry. The proliferation was expressed as the ratio of intimal area to total vascular area [I/(I + M)], (Figs. 2, 3).Local exposure to IGF-I following donor harvesting but prior to transplantation, with no systemic administration of IGF-I, results in increased cell proliferation and accelerated TA in vivo, suggesting an important role for IGF-I in TA.