This National Science Foundation funded study is investigating novel pedagogies for helping teachers infuse inquiry into a standards-based science curriculum. Using a Multi-User Virtual Environment (MUVE) as a pedagogical vehicle, teams of middle school students are asked to collaboratively solve a simulated 19th century city's problems with illness, through interaction with each others' “avatars”, digital artifacts, tacit clues, and computer-based “agents” acting as mentors and colleagues in a virtual community of practice. This paper describes the results from the first of three implementations in 2004 with more than 1000 students from geographical diverse urban areas. Results indicate that our curriculum is motivating and improves content knowledge and inquiry skills as compared to a similar paper-based curriculum.