The objectives of this study were to: examine the potential interaction between students' epistemological beliefs and placement in a simulation condition (constructivist versus non-constructivist) on conceptual development; and to assess whether a constructivist computer simulation experience would result in a greater degree of conceptual change than a non-constructivist simulation experience. The sample consisted of approximately 250 non-biology majors enrolled in a human anatomy and physiology survey course at a large midwestern university. Fourteen sections of approximately 15 students each were randomly assigned to one of two conditions: (1) a confirmatory simulation condition in which students used a cardiovascular simulation in prescribed steps to resolve a set of 12 cases or; (2) an exploratory simulation condition in which the same cardiovascular simulation was used in a constructivist setting. Students with greater epistemological sophistication were found to do better in the exploratory simulation environment while students with less sophisticated beliefs about knowledge and learning achieved best in the more prescribed, confirmatory simulation environment. Additionally, this study provided evidence that an exploratory (constructivist) simulation experience could be more effective in altering learners' misconceptions than a confirmatory experience. (Contains 19 references.) (AEF)