The aim of this research was to develop a model of factors affecting students' ability to interpret external representations (ERs) in biochemistry. The study was qualitative in design and was guided by the modelling framework of Justi and Gilbert. Application of the process outlined by the framework, and consultation with relevant literature, led to the expression of a Venn model and to the formulation of operational definitions for seven component factors of the model; namely, the conceptual (C), reasoning (R), representation mode (M), reasoning-mode (R-M), reasoning-conceptual (R-C), conceptual-mode (C-M), and conceptual-reasoning-mode (C-R-M) factors. To validate the model, nine students were interviewed using a specially designed "three-phase single interview technique" to investigate their interpretation of three ERs, representing antibody-antigen interaction. The data were analysed by induction, where response patterns emerged naturally rather than being predisposed. The results verified the validity of the expressed model and its component factors. We suggest that the model has a range of potential applications, including as a tool for framing researchers' thinking about students' difficulties with, and interpretation of, scientific ERs, and for the design of strategies to improve learning with ERs. (Contains 7 figures and 1 note.)