We present the circumstances surrounding a 57-year-old Caucasian man with advanced colorectal cancer who developed relapsing interstitial lung disease following a single exposure to irinotecan (CPT-11). Progressive pulmonary insufficiency and death were reported in the initial Japanese studies, despite institution of empiric steroid therapy for a syndrome similar to that which our patient experienced. As a result, patients with compromised pulmonary function were generally excluded from US clinical trials. Notwithstanding this, cough and dyspnea were reported in approximately 20% of patients in the US studies. As the clinical indications for the use of this agent expand, we describe irinotecan-associated interstitial pneumonitis as a serious potential adverse effect. Patients with pre-existing pulmonary disease may be at higher risk for this complication and clinicians should be alert to this possibility.