Think-aloud and pre-test data were collected from 49 undergraduates with varying levels of prior domain knowledge to examine the relationship between prior domain knowledge and self-regulated learning with hypermedia. During the experimental session, each participant individually completed a pretest on the circulatory system, and then one 40-min hypermedia learning task during which he or she learned about the circulatory system. Think-aloud data were collected during the 40-min learning task to measure each participant's use of specific self-regulated learning processes related to planning, monitoring, and strategy use. Results indicate that prior domain knowledge is significantly related to how the participants self-regulated their learning during the 40-min learning task with hypermedia. Specifically, prior domain knowledge is positively related to participants' monitoring and planning and negatively related to their use of strategies during the hypermedia learning task.