Over the past 5 years we have recognized a new pulmonary complication of hematopoietic stem cell transplantation (HSCT) associated with fever and pulmonary nodules termed 'pulmonary cytolytic thrombi' (PCT). Retrospective analysis of medical and radiographic records and pathologic material from 13 HSCT recipients with PCT and a review of the Blood and Marrow Transplant Database for all patients with radiographic evidence of pulmonary nodules or who underwent open-lung biopsy from 1 January 1993 to 31 December 1998 (n = 1228) were performed. The median age of patients with PCT was 11.9 years (range, 1.3-29.7 years). All patients developed fever at a median of 72 days (range, 8-343 days) post transplant, followed by pulmonary nodules on chest CT. Eleven patients were receiving therapy for active GVHD (acute, grades I-IV (n = 10); extensive chronic (n = 1)). Biopsy of the pulmonary nodules revealed a unique pattern of necrotic, basophilic thromboemboli with amorphous material suggestive of cellular breakdown products. This was descriptively labeled 'pulmonary cytolytic thrombi'. Immunohistochemical staining revealed entrapped leukocytes and disrupted endothelium, but was negative for histiocytes. Cultures and immunohistochemical stains were negative for infectious agents. Empiric therapy included systemic corticosteroids (n = 9) and amphotericin (n = 7). Nine patients survive with resolution of PCT at a median follow-up of 1.5 years. Bone Marrow Transplantation (2000) 25, 293-300.