Indocyanine green (ICG) is generally considered to be safe for IV administration and has a very low incidence of complications. We report 2 cases of severe hypotension immediately after low dose administration of IV ICG. The first case is a 69-year-old woman who developed severe hypotension after a second 5 mg IV bolus of ICG given shortly after the placement of an aneurysm clip during an otherwise uneventful surgery performed under general anesthesia. The second case is a 56-year-old woman with moyamoya disease who became hypotensive subsequent to a 2.5 mg ICG bolus at the conclusion of an external-carotid to internal-carotid bypass procedure under general anesthesia. Anesthesiologists and surgeons are increasingly likely to encounter or request the intraoperative administration of ICG, and they need to be aware of this potential for an adverse reaction, particularly with the repeated doses. Anesthesia and other intraoperative conditions may mask the typically mild adverse reactions usually associated with ICG.