Abstract: We present two patients with subcutaneous fat necroses (SCFN) in whom endocrinologie studies revealed an association with elevated prostaglandin E (PGE) levels. A boy born after prolonged labor complicated by meconium aspiration developed erythematous, indurated plaques over the back, arrns, buttocks, and cheeks at 4 days of age. A biopsy specimen of involved skin showed panniculitis with foei of necrotic adipocytes containing radially arranged, needle-shaped clefts and a granulomatous infiltrate in the septae. Laboratory studies revealed hypercalcemia of 13.6 mg/dl (normal 8.8–10,1 mg/dl), eievated 1,251,25(OH)2D3, and increased urinary excretion of PGE2. The child was hospitalized and treated with systemic steroids and diuretics, with resolution of SCFN and hypercalcemia. The second patient was a girl born with cyanotic heart disease. A diagnosis of Ebstein anomaly was made, and intravenous PGE, was started to keep patent the ductus arteriosus. Four days later erythematous, indurated plaques were noted on the knee, back, and anterior chest. A skin biopsy specimen revealed SCFN. There was no associated laboratory abnormality. On discontinuing PGE, no new tesions formed and the existing panniculltis resolved. These two cases demonstrate the association between SCFN and eievated PGE levels (endogenous in patiënt 1, exogenous in patiënt 2). No previous reports of SCFN after the administration of PGE, have appeared in the literature.