In this study, we used think-aloud verbal protocols to examine how various macro-level processes of self-regulated learning (SRL; e.g., planning, monitoring, strategy use, handling of task difficulty and demands) were associated with the acquisition of a sophisticated mental model of a complex biological system. Numerous studies examine how specific micro-level SRL processes such as judgments of learning or prior knowledge activation are related to learning outcomes. However, it is also valuable to look at these processes in macro-level aggregates because efficacy and use of micro-level strategies can vary due to individual differences. Two hundred and nineteen high-school and middle-school students produced think-aloud protocols while learning with a hypermedia environment. We transcribed and coded participants' learning sessions for the use of micro- and macro-level SRL processes. Participants' developmental level, prior knowledge, and monitoring behaviors were associated with posttest mental model sophistication. These results illustrate that monitoring is a key SRL process when developing an understanding of a complex science topic using hypermedia. (Contains 2 tables.)