Sixty-two high-school biology students, paired heterogeneously based on prior knowledge, learned about genetic using GenScope, a computer-based learning environment (CBLE), over four 90-minute class periods. Differences between low and high prior knowledge students emerged with convergence of verbal process data and pre- and post-test product data. The low prior knowledge students gained significantly in conceptual understanding from pre- to post-test, whereas the high prior knowledge students' understanding did not significantly change. In an analysis of their verbalizations, low prior knowledge students regulated their learning by relying on their partners for cognitive and other regulatory support whereas the high prior knowledge students spent most of their time regulating their own learning or providing external support for their lower prior knowledge peer. The results of this naturalistic study can potentially be used to inform educational practice by highlighting scaffolds that may foster self-regulated learning in a CBLE-mediated science inquiry context.