Diagrams can serve as representational models in scientific research, yet important questions remain about how they do so. I address some of these questions with a historical case study, in which diagrams were modified extensively in order to elaborate an early hypothesis of protein synthesis. The diagrams’ modelling role relied mainly on two features: diagrams were modified according to syntactic rules, which temporarily replaced physico-chemical reasoning, and diagram-to-target inferences were based on semantic interpretations. I then explore the lessons for the (...) relative roles of syntax, semantics, external marks, and mental images, for justifying diagram-to-target inferences, and for the “artefactual approach” to scientific models. (shrink)