In the process of designing and field-testing bioinformatics curriculum materials, we have adopted a three-stage, progressive model that emphasizes collaborative scientific inquiry. The elements of the model include: (1) context setting, (2) introduction to concepts, processes, and tools, and (3) development of competent use of technologically sophisticated tools. A curriculum involving the analysis of HIV sequence data is used to illustrate this framework and provide a context for discussing this student-centered, inquiry-based approach to bioinformatics education and literacy. (Contains 6 figures.)