We used the fluorescent dye Fluoro-Jade, capable of selectively staining degenerating neurons and their processes, in order to analyze degenerative effects of transecting the hippocampus from its main input, the entorhinal cortex in vivo and in organotypical hippocampal slice culture. Degenerating fibers stained with Fluoro-Jade were present as early as 1 day postlesion in the outer molecular layer of the dentate gyrus and could be detected up to 30 days postlesion. However, the intensity of the Fluoro-Jade staining in the outer molecular layer faded from postlesional day 20 onward. Punctate staining, various cells and neural processes became visible in this area suggesting that degenerating processes were phagocytosed by microglial cells or astrocytes. We conclude that Fluoro-Jade is an early and sensitive marker for studying degenerating neurites in the hippocampal system.