A 33-year-old man with a nonatherosclerotic vasculopathy of undetermined origin had progressive occlusive disease of the lower limb vessels. The resultant severe rest pain and ischemic ulceration of his foot were inoperable and unresponsive to conventional drug therapy. Treatment was begun with intra-arterially administered alprostadil (prostaglandin E1), a vasodilator and inhibitor of platelet aggregation. Although immediate benefit was equivocal, his rest pain had disappeared six weeks after infusion, and the ischemic ulcer almost healed completely. Blood flow studies showed increased flow to the feet, consistent with the subjective improvement. The beneficial effect of alprostadil suggests that further studies with this agent are warranted for patients with nonatherosclerotic vasculopathy.