Whether Ca 2ϩ released from stores within the presynaptic nerve terminals also contributes to the Ca 2ϩ elevation evoked by action potentials was tested in intact bullfrog sympathetic ganglia. Intraterminal Ca 2ϩ transients (⌬[Ca 2ϩ ] i ) were evoked by electrical shocks to the presynaptic nerves at 20 Hz and were monitored by fura-2 fluorimetry. Ca 2ϩ released through intraterminal ryanodine-sensitive channels accounted for 46% of the peak Ca 2ϩ elevation. Moreover, in half of the terminals when intraterminal release was blocked by ryanodine, ⌬[Ca 2ϩ ] i reached a plateau at 200 Ϯ 24 nM. Because 20 Hz is a frequency favorable for the release of a neuropeptide, luteinizing hormone releasing hormone (LHRH) from these presynaptic nerve terminals, and because the threshold level for LHRH release is 186 nM, intraterminal Ca 2ϩ release during nerve firing is likely to play a major role in regulating LHRH release. The intraterminal ryanodine channels were facilitated by caffeine as in other tissue. The releasable ryanodine-sensitive store could elevate the intraterminal [Ca 2ϩ ] by an amount as high as 1.6 M at a rate as fast as 250 nM/sec. The store could be refilled within 100 sec after a maximal discharge of its content by 20 Hz firing. Oscillation of [Ca 2ϩ ] i evoked by 20 Hz nerve firing occurred in normal Ringer solution, in ryanodine, and in caffeine with a periodicity of ϳ10 sec. Besides the facilitatory effects on the ryanodine-sensitive channels, caffeine also had inhibitory effects on ⌬[Ca 2ϩ ] i via its action on a different process.