Neurotrophins (NGF, BDNF) elicit significant elevation of cAMP as well as IP3-concentrations in either membrane preparations or intact isolated nerve endings from rat brain hippocampus. The induced second messenger responses in membrane preparations were detectable in the subsecond time range. The IP3-level reached a maximum after a few hundred ms; whereas the cAMP-level continued to rise even after several seconds. The IP3-response but not the cAMP-signal was inhibited in the presence of the tyrosine kinase blocker K252a, suggesting that the two second messenger cascades were triggered via different mechanisms. The results suggest that neurotrophins may induce short-term effects in nerve terminals via second messenger pathways.