A 52-year-old man with stage IV rectal carcinoma with neuroendocrine differentiation on liver biopsy recently completed an 8-cycle course of cisplatin, 60 mg/m2, and etoposide phosphate, 120 mg/m2, over a 6-month period. Five weeks after cisplatin and etoposide therapy, cycle 1 of the FOLFIRI regimen and bevacizumab was initiated. Dosing consisted of irinotecan, 180 mg/m2; leucovorin, 400 mg/m2; fluorouracil, 400 mg/m2 (intravenous push); fluorouracil, 2400 mg/m2 (infused); and bevacizumab, 5 mg/kg. On day 11 after the FOLFIRI/bevacizumab infusion, the patient was hospitalized for neutropenic fever, thrombocytopenia, anemia, and diarrhea. On day 15, the patient awoke with a headache and bilateral cortical blindness. Magnetic resonance imaging revealed patchy areas of increased fluid-attenuated inversion recovery signal intensity in the occipital and posterior parietal lobes, consistent with RPLS (Figure 1). The patient's blood pressure during hospitalization was mildly elevated (systolic blood pressure range, 140-150 mm Hg), which was aggressively treated subsequent to the vision loss. A qualitative urine assessment revealed proteinuria, which was not present before the initiation of FOLFIRI/bevacizumab chemotherapy. Other laboratory values included hematocrit, 28.3% (pre-FOLFIRI/bevacizumab therapy level, 28.6%), which was normal; serum urea nitrogen and creatinine levels were also measured, liver function testing was performed, and a peripheral blood smear was obtained. On day 17, the patient developed transcortical global aphasia with intermittent spells of confusion and agitation. By day 18, his speech and visual disturbance began to improve. On day 19, he experienced a generalized tonic-clonic seizure. A diagnostic lumbar puncture showed a normal opening pressure and normal cerebrospinal microscopic and biochemistry results. Subsequent magnetic resonance imaging on day 19 showed interval improvement in fluid-attenuated inversion recovery hyperintensities (Figure 2). By day 25, the patient's neurologic deficits had completely resolved.