It has been shown that both amygdaloid and hippocampal kindling induce sprouting of the messy fibers in the dentate gyrus. In this study, we investigated whether non-epileptogenic stimulation could also induce messy fiber sprouting. Long-term potentiation (LTP) was induced in the dentate gyrus by the application of brief, high-frequency trains to the perforant path. The potentiating stimulation was applied each day for 10 days, and the tissue was prepared for Timm labelling 7 days later. Sprouting was significantly increased in the LTP group compared to the implanted control rats. These results suggest that messy fiber sprouting is not damage-induced and is dependent on neuronal activation. (C) 1997 Elsevier Science B.V.