Sirolimus-associated pulmonary disease should be considered in the differential diagnosis of acute respiratory distress syndrome in transplant recipients receiving this drug. It represents a rare, potentially lethal, and yet reversible adverse effect. We report the case an infant who presented with acute respiratory distress 57 days after heart transplantation 3 days after starting sirolimus. The acute presentation and prompt resolution after discontinuation of this drug suggest a direct toxic effect to the lungs. To our knowledge, this is the first published pediatric description of this syndrome after heart transplantation.