Educators are recognizing the potential power of immersive virtual reality (IVR) to allow learners to experience previously intangible firsthand phenomena, such as atoms and molecules. In this study, an IVR simulation of a complex gene regulation system was co-designed with an undergraduate microbiology course instructor. The course, with 234 students, was taught using active learning strategies, including peer instruction and exposure to a two-dimensional computer simulation. Thirty-four students from the course participated in an interactive IVR experience using head-mounted displays. We assess students' conceptual understanding using tests, multimodal data collected during the IVR sessions (including video analysis in combination with physiological sensor data and eye-tracking data) as well as semi-structured interviews. We found that students who were seated while in IVR demonstrated significantly higher conceptual understanding of gene regulation at the end of the course and higher overall course outcomes, as compared to students who experienced the course as originally designed (control). However, students who experienced IVR in a standing position performed similarly to the control group. In addition, learning gain appears to be influenced by a combination of prior knowledge and how IVR is experienced (ie, sitting vs. standing). Learning implications for the connections between sensorimotor systems and cognition in IVR are discussed.