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Reading strategies, prior knowledge and cognitive load are some variables that have been related with comprehension and learning with hypertext systems. In this study we analyze the effect of two different hypertext reading strategies – coherence and interest – and two prior knowledge levels – low and high - on cognitive load, and their relation with learning. For low prior knowledge readers, data reveal that following a coherence strategy leads to lower cognitive load during reading and better learning. For high prior knowledge readers, following an interest strategy produce higher cognitive load during reading than a coherence strategy, but they learned equally from both strategies. These results are discussed taking into account the implication of two different components of cognitive load (extraneous and germane cognitive load).