One of the important goals of problem-based learning (PBL) in medical education is to enhance medical students' clinical reasoning--hypothetico-deductive reasoning (HDR) in particular--through small group discussions. However, few studies have focused on explicit strategies for promoting students' HDR during group discussions in PBL. This paper proposes a novel conceptual framework that integrates Toulmin's argumentation model (1958) into Barrows's HDR process (1994). This framework explains the structure of argumentation (a claim, data, and a warrant) contextualized in each phase of HDR during PBL. This paper suggests four instructional strategies--understanding argument structures, questioning, elaborating on structural knowledge, and assessing argumentation--for promoting medical students' argumentation in relation to HDR processes. Further implications of the proposed framework for other disciplines, such as science, legal, and engineering education, are also discussed.