Two small neonates, one with hypoplastic right heart syndrome, and the other with tetralogy of Fallot and pulmonary atresia, were treated with intravenous prostaglandin E1 (Prostyn VR, Upjohn, Kalamazoo, Michigan) for 96 and 33 days, respectively. They developed limited cortical hyperostosis, but marked soft tissue swellings in all extremities. The changes were noted after PGE1 treatment for four weeks and one week, respectively. A skin biopsy was performed in one patient and revealed edematous changes and arteriolar wall abnormalities. We add this peripheral hard edema to the list of complications of PGE1 therapy, and speculate as to its pathophysiology.