This study investigated 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 collaboratively solved problems around disease in a virtual town called River City. The students interacted with ‘avatars’ of other students, digital artefacts and computer-based ‘agents’ acting as mentors and colleagues in a virtual community of practice set during the time period when bacteria were just being discovered. This paper describes the results from three implementations of the River City virtual environment in 2004–05 with approximately 2000 students from geographically diverse urban areas. The results indicated that students were able to conduct inquiry in virtual worlds and were motivated by that process. However, the results from the assessments varied depending on the assessment strategy employed.