Possible modulatory actions of endogenous neurotransmitters on long-term potentiation (LTP) were investigated in the fimbria-CA3 pathway of rat hippocampal slices. Bath application of atropine (10 microM), but neither timolol (10 microM) nor D,L-2-amino-3-phosphonopropionate (AP3, 100 microM), significantly attenuated LTP induced by 20 pulses of 50 Hz stimulation. When stronger stimulation (3 trains of 100 Hz, 100 pulses) was used for the induction of LTP, timolol significantly attenuated LTP, but atropine and AP3 did not. These results suggest that, under specified conditions, endogenous acetylcholine through muscarinic receptors, and noradrenaline through beta-adrenergic receptors may modulate the generation of LTP in the fimbria-CA3 pathway. Metabotropic glutamate receptors may be involved not in the generation of LTP but in low-frequency synaptic transmission, since 300-1,000 microM AP3 greatly reduced, or abolished synaptic transmission in this pathway.