In the study reported here, the authors assessed the use of efficient organization of knowledge and of problem-solving strategies to enhance medical students' clinical problem-solving skills. Thirty-five preclinical medical students were randomly assigned to a experimental or control group and given a knowledge base containing information on eight congenital heart diseases to learn. Information for the experimental group emphasized disease groupings (based on their similar clinical presentation), symptom-disease associations, and clinical problem-solving heuristics. The same information for the control group was presented in a textbook format that emphasized the pathophysiology of the diseases. The students then diagnosed three computerized diagnostic problems of varying difficulty while verbalizing their problem-solving strategies. The results showed that the experimental group acquired a higher ratio of diagnostic to nondiagnostic cues, mentioned the correct diagnosis sooner in their workups, and correctly diagnosed the most difficult case more often than the control group. These results provide support for revisions in the organization and presentation of information that are aimed at improving clinical problem-solving skills.