In this exploratory study, we examined how students with high and low levels of self-regulation responded to, and approached learning from, case-based instruction. Fifty-eight first-year veterinary students, enrolled in a case-based biochemistry laboratory course, were classified according to their precourse performances on two self-regulated learning inventories. Nine students, representing high and low levels of self-regulation, were interviewed three times during the semester to explore initial and changing responses and approaches to case-based instruction. Students' responses are described in terms of the motivational components of case-based instruction: the interest expressed, the value students perceived in case-based instruction, as well as their confidence for leaning from the case method. Students' approaches are described in terms of their goal orientations, evaluative lens, levels of self-awareness, openness to challenges, perceived levels of relevant knowledge, and contextual vulnerability.