Organic chemists must understand the 3-D structure of molecules and be adept at relating different 2-D diagrammatic representations of molecules. Concrete (3D) models can aid chemistry students in developing these aspects of representational competence. A growing trend is to incorporate 3D virtual models into instruction. In two studies, we tested the relative effectiveness of concrete and virtual models when relating molecular representations. Participants completed tasks that involved matching either virtual or concrete models to three different types of molecular diagrams. There were no differences in accuracy for virtual and concrete models, but participants performed significantly faster with virtual models. The benefit likely resulted from the hand-held computer interface, which constrained interactivity to make the most task-relevant information salient. These results highlight the importance of interface design in promoting effective use of spatial representations, and suggest a potential benefit of teaching with virtual models rather than traditional media in chemistry.