Cyclosporine is the core component of all immunosuppressive protocols. Renal insufficiency and hypertension are the two major side effects of cyclosporine use. A vascular effect of cyclosporine could explain these complications. To study the effect of cyclosporine on vessel wall, a model of isolated renal and femoral artery perfusion was used in the dog. The injection of 0.5, 1, 5 and 10 mg of cyclosporine in the renal artery caused an average increase in renal perfusion pressure of 8 +/- 4, 15 +/- 8, 32 +/- 12 and 81 +/- 21 mmHg (p less than 0.05) respectively. Blockade of alpha-adrenergic receptors and renal sympathectomy did not modify the renal vascular response to cyclosporine. The injection of 1, 5, 10 and 20 mg of cyclosporine in the femoral artery caused an average increase in perfusion pressure of 4 +/- 2, 10 +/- 4, 9 +/- 2 and 20 +/- 8 mmHg (p less than 0.05) respectively. Blockade of alpha-adrenergic receptors and lumbar sympathectomy prevented the vasoconstrictive effect of cyclosporine on the femoral artery. Therefore, cyclosporine caused a significant increase in renal perfusion pressure and a modest vasoconstriction of the femoral artery. This effect appears to be related to an adrenergic mechanism only in the femoral circulation. We conclude that other studies are needed to define the mechanism responsible for the vasoconstrictive effect of cyclosporine.