Objective: To describe a patient with reversible posterior leukoencephalopathy syndrome following the administration of bevacizumab (Avastin), a monoclonal antibody against vascular endothelial growth factor. Design: Case report/literature review. Setting: University hospital. Patient: A 52-year-old man receiving chemotherapy for stage IV rectal carcinoma. Results: Clinical and radiographic evidence consistent with reversible posterior leukoencephalopathy syndrome was found following the administration of irinotecan hydrochloride, leucovorin calcium, and fluorouracil (FOLFIRI) regimen chemotherapy and bevacizumab. Conclusions: Reversible posterior leukoencephalopathy syndrome following treatment with angiogenesis modulators can occur. In addition to raising clinical suspicion in appropriate patients, this report may yield clues to the pathophysiologic underpinnings of reversible posterior leukoencephalopathy syndrome.