One of the challenges of science education is for students to develop scientific knowledge that is personally meaningful and applicable to real-life issues. This article describes a middle-school science intervention fostering adolescents' critical reasoning in the context of HIV by strengthening their conceptual understanding of HIV biology. The intervention included two components: critical reasoning activities that fostered knowledge integration and application to real-world problem solving, and science writing activities that promoted argument building. Two seventh-grade classes participated in the study. One class participated in the critical reasoning and writing activities (CR&W); the other class participated in critical reasoning activities only (CR group). Results demonstrate significant pre- and posttest improvements on measures of students' HIV knowledge, HIV understanding, and critical reasoning about realistic scenarios in the context of HIV, with the improvements being greater in the CR&W group. The discussion focuses on the role of conceptual knowledge in health reasoning, the role of science writing in fostering knowledge integration, and the benefits of a “thinking curriculum” approach to integrated health and science education. © 2007 Wiley Periodicals, Inc. J Res Sci Teach 44: 844–863, 2007