1. Long-term potentiation of quantal secretion was studied at ciliary ganglion synapses of post-hatched birds following tetanic stimulation of the oculomotor nerve and the effects of nitric oxide (NO) on quantal secretion were determined. 2. Tetanic stimulation of the oculomotor nerve at 30 Hz for 20 s at room temperature increased the amplitude of the excitatory postsynaptic potential (EPSP) by about 100%; 1-2 min after the tetanus the EPSP declined exponentially with a time constant of about 10 min (long-term potentiation; LTP). LTP was due to an increase in the quantal content of the EPSP not to a change in quantal size. 3. A component of LTP was shown to be due to the release of NO in the ganglion, as blocking the synthesis of NO with L-arginine methyl ester decreased the potentiation by 70%. 4. Exogenous application of NO using sodium nitroprusside increased the amplitude of the EPSP by more than 30% due to an increase in the quantal content of the EPSP. 5. Both 8-bromo-cGMP and 8-bromo-cAMP increased the quantal content of the EPSP by more than 44% without changing the quantal size. 6. The results suggest that endogenous NO is involved in either the initiation or maintenance phase of LTP. This may occur through an increase in quantal secretion consequent on the action of an elevated cGMP increasing cAMP.