OBJECTIVE To evaluate the safety and effect of systemic anti-vascular endothelial growth factor bevacizumab (Avastin) in treatment of exudative retinal detachment secondary to choroidal melanoma. METHODS Two patients were definitively treated with ophthalmic plaque radiation therapy and subsequently given 10 mg/kg intravenous bevacizumab every 2 weeks for 3 or 4 cycles. RESULTS Complete resolution of the exudative retinal detachments occurred 1.2 months and 6.5 months after completion of systemic bevacizumab and 4.7 and 10 months after plaque therapy. The first patient's visual acuity improved from counting fingers at 1 foot to 20/80 (at 40 months), while his tumor regressed from 9.2 to 3.7 mm in apical height. The second patient's initial acuity was 20/20 and final acuity was 20/80 (at 35 months), while her tumor height regressed from 12.2 to 6.3 mm. No exudative retinal detachment, intraocular or systemic tumor recurrence was noted up to 40 and 35 months, respectively. Acute side effects of intravenous bevacizumab therapy included hypertension, headaches, and amenorrhea, which shortly resolved after completion of therapy. CONCLUSIONS This pilot study suggests that systemic bevacizumab was associated with transient systemic effects as well as resolution of choroidal melanoma-related exudative retinal detachment.