The present study was conducted to investigate qualitative changes that occur in the structure of knowledge in acquiring medical expertise. Therefore, the representation of pathophysiological knowledge was compared in subjects at four different levels of expertise. Subjects studied four clinical cases under three different time constraints, and provided a diagnosis and a pathophysiological explanation for the signs and symptoms in each case. Both diagnostic accuracy and quality of explanations increased with level of expertise. The explanations of experts, however, were less elaborate and less detailed than those of students. Constraining processing time affected the quality of explanations of advanced students, but not that of experts; conversely, the elaborateness and level of detail of explanations was affected in experts but not in students. The findings are explained by a network model integrating the two-world hypothesis in which biomedical and clinical knowledge are organised as two worlds apart (Patel, Evans, & Groen, 1989a, b) and the hypothesis of knowledge encapsulation in which biomedical knowledge becomes encapsulated into clinical knowledge (Schmidt & Boshuizen, 1992).