The differential diagnosis of pulmonary infiltrates after solid-organ transplantation presents a broad differential diagnosis including opportunistic infections and drug-induced lung disease. We report an adult liver transplant recipient who had breathlessness and pulmonary infiltrates following the introduction of sirolimus, and in whom transbronchial biopsy demonstrated a granulomatous interstitial pneumonitis and an organizing pneumonia with a CD4 T-cell infiltrate suggesting a T-helper cell-associated reaction to a processed sirolimus protein complex. Withdrawal of sirolimus produced a rapid clinical and radiologic improvement. This case indicates that with the increasing use of sirolimus, clinicians need to be aware of pulmonary hypersensitivity from this agent.