Semantic memory has been investigated in numerous neuroimaging and clinical studies, most of which have used verbal or visual, but only very seldom, musical material. Clinical studies have suggested that there is a relative neural independence between verbal and musical semantic memory. In the present study, "musical semantic memory" is defined as memory for "well-known" melodies without any knowledge of the spatial or temporal circumstances of learning, while "verbal semantic memory" corresponds to general knowledge about concepts, again without any knowledge of the spatial or temporal circumstances of learning. Our aim was to compare the neural substrates of musical and verbal semantic memory by administering the same type of task in each modality. We used high-resolution PET H(2)O(15) to observe 11 young subjects performing two main tasks: (1) a musical semantic memory task, where the subjects heard the first part of familiar melodies and had to decide whether the second part they heard matched the first, and (2) a verbal semantic memory task with the same design, but where the material consisted of well-known expressions or proverbs. The musical semantic memory condition activated the superior temporal area and inferior and middle frontal areas in the left hemisphere and the inferior frontal area in the right hemisphere. The verbal semantic memory condition activated the middle temporal region in the left hemisphere and the cerebellum in the right hemisphere. We found that the verbal and musical semantic processes activated a common network extending throughout the left temporal neocortex. In addition, there was a material-dependent topographical preference within this network, with predominantly anterior activation during musical tasks and predominantly posterior activation during semantic verbal tasks.