In 2 experiments we examined the role of (a) specificity, (b) the type of targeted learning activities, and (c) learners' prior knowledge for the effects of relevance instructions on learning from instructional explanations. In Experiment 1, we recruited novices regarding the topic of atomic structure (N = 80) and found that "specific" relevance instructions designed to focus learners' attention on basic contents (i.e., focused processing prompts) were more effective than "general" relevance instructions that merely told learners to process the explanations for study purposes. This "specificity effect" was mediated by lower extraneous load that was due to having to identify the relevant information. Furthermore, regarding the role of the type of targeted learning activities, we found that focused processing prompts were more effective when they were combined with reduced explanations without explicit answers to the focused processing prompts, rather than with complete explanations that included them. This effect was mediated by a higher amount of generative learning activities on the part of the learners who received reduced explanations. To explore the role of learners' prior knowledge, in Experiment 2 we recruited a sample with greater diversity in prior knowledge (N = 77). As in Experiment 1, we found that reduced explanations and focused processing prompts were more effective than complete explanations and general purpose instructions for novice learners. However, learners with a higher degree of prior knowledge benefited more from complete explanations and general purpose instructions than from reduced explanations and focused processing prompts.