New technological and cultural developments surrounding adolescents' use of the World Wide Web offer an opportunity for turning aspects of the Internet gaming phenomenon to the advantage of neuroscience education. Specifically, an experimental project to transmit aspects of problem-based learning and the National Science Standards through an interactive Web adventure is reported here. The Reconstructors is an episodic Web-based adventure series entitled Medicinal Mysteries from History. It is funded by the National Institute on Drug Abuse, and the first series focuses on opioids. It was created with the input of middle school students and teachers. Through the use of multimedia technologies, middle school students enter a futuristic world in which they become "reconstructors," members of an elite scientific unit charged with recovering lost medical knowledge about analgesic drugs. Two of the four episodes have been evaluated through a comprehensive review process involving middle school students, teachers, neuroscience researchers, and clinicians. Analysis of the pretest and posttest scores demonstrated significant knowledge gain that validly can be attributed to use of the game. These data provide evidence that science content can be transmitted through innovative online techniques without sacrificing compelling content or effective pedagogical strategies.