This study examines the benefits of reading strategy training on adolescent readers' comprehension of science text. Training was provided via an automated reading strategy trainer called the Interactive Strategy Trainer for Active Reading and Thinking (iSTART), which is an interactive reading strategy trainer that utilizes animated agents to provide reading strategy instruction. Half of the participants were provided with iSTART while the others (control) were given a brief demonstration of how to self-explain text. All of the students then self-explained a text about heart disease and answered text-based and bridging-inference questions. Both iSTART training and prior knowledge of reading strategies significantly contributed to the quality of self-explanations and comprehension. Adolescents with less prior knowledge about reading strategies performed significantly better on text-based questions if they received iSTART training. Conversely, for high-strategy knowledge students, iSTART improved comprehension for bridging–inference questions. Thus, students benefitted from training regardless of their prior knowledge of strategies, but these benefits translated into different comprehension gains.