- "Dream on, detectives. You've got me under control for now, but there's a meltdown coming soon, and her name is Carmen Sandiego."
Jane Reaction is an evil engineer, using her skills for her own wicked ends. She was a respected chemical engineer until someone told her that engineers weren't real scientists. Jane went critical and suffered a personal meltdown. She joined V.I.L.E. after that. She now fights scientists with her doom machines and makes evil robots which capture people.
She appears as an engineer with a white labcoat and has glasses.
After the jailbreak at ACME jail, Jane went to 1460 and stole the accounting kipues from the Inca Empire, under the reign of Pachacuti. The player, along with Ann Tickwittee, found her hiding in a sack of Incan silver and took her back to ACME jail.
- Her name is a pun on the term "chain reaction".