Research on expert-novice differences has mainly focused on how experts solve familiar problems. We know far less about the skills and knowledge used by experts when they are confronted with novel problems within their area of expertise. This article discusses a study in which verbal protocols were taken from subjects of various expertise designing an experiment in an area with which they were unfamiliar. The results showed that even when domain knowledge is lacking, experts solve a novel problem within their area of expertise by dividing the problem into a number of subproblems that are solved in a specified order. The lack of domain knowledge is compensated for by using abstract knowledge structures and domain-specific heuristic strategies. However, the quality of their solutions is considerably lower than the quality attained by experts who were familiar with the type of problem to be solved. The results suggest that when experts are confronted with novel problems as compared with familiar problems, their form of reasoning remains intact, but the content of their reasoning suffers due to lack of domain knowledge.