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In two studies the role of biomedical knowledge in the diagnosis of clinical cases was explored. Experiment 1 demonstrated a decrease in the use of biomedical knowledge with increasing expertise. This result appeared to be at variance with some findings reported in the literature (e.g., Lesgold, 1984), but supported those of others (e.g., Patel, Evans, & Groen, 1989). In Experiment 2, three possible explanations for this phenomenon were investigated: (1) rudimentation of biomedical knowledge, (2) inertia, and (3) encapsulation of biomedical knowledge under higher order concepts. Using a combined think-aloud and post-hoc explanation methodology, it was shown that experts have more in-depth biomedical knowledge than novices and subjects at intermediate levels of expertise. The findings generally support a three-stage model of expertise development in medicine consisting of acquisition of biomedical knowledge, practical experience, and integration of theoretical and experiental knowledge resulting in knowledge encapsulation.