Multimedia integration signals highlight correspondences between text and pictures with the aim of supporting learning from multimedia. A recent meta-analysis revealed that only learners with low domain-specific prior knowledge benefit from multimedia integration signals. To more thoroughly investigate the influence of prior knowledge on the multimedia signaling effect in a more ecologically valid context, we conducted a quasi-experimental field study with 8th graders. They learned with a digital multimedia textbook in 1 of the 2 versions: (a) a basic version with signals that supported only the selection and organization of information from either text or pictures or (b) an extended version with additional multimedia integration signals to support the integration of information from text and pictures (e.g., color coding, deictic references). Results of a contrast analysis revealed that low-prior-knowledge learners learned better with the extended version compared with the basic version, whereas adding multimedia integration signals was detrimental for learning outcomes of high-prior-knowledge learners. This expertise reversal effect could only partially be explained by cognitive load measures, in that high-prior-knowledge learners had higher extraneous cognitive load in the condition with multimedia integration signals. The results suggest a need for a more individualized multimedia design that considers students' prior knowledge.