Educational researchers and policy-makers have for some time touted the need for interdisciplinary teaching. However, despite this desire for a change towards interdisciplinary teaching, teachers are often uncertain about how to go about planning, implementing, and sustaining interdisciplinary teaching programs. This is partly due to the lack of a framework for integrating productive ideas across the disciplines. This paper focus on how to grasp the challenges of an interdisciplinary approach to teaching in mathematics and the subjects of natural science. Based on contemporary mathematics and science education we design a didactical framework for interdisciplinary teaching centered on modeling activities across mathematics and the disciplines of natural science. To exemplify the potential of the framework we present a case study of an intensive in-service teacher-training program for mathematics and biology teachers. The teachers were presented to the didactical framework and in pairs of two, one mathematics teacher and one biology teacher; they designed and implemented interdisciplinary mathematicsbiology teaching sequences. The teachers’ reports on their development and implementation of the teaching sequences and presentations given at a final seminar show that in general it is possible for the teachers from two discplines to plan, carry through, evaluate and report about interdisciplinary modeling activities.