1. Intracellular and focal extracellular recording techniques were used to study neurotransmitter release mechanisms in postganglionic sympathetic nerve terminals in the guinea-pig isolated vas deferens. 2. High concentrations of the selective N-type calcium channel blocker omega-conotoxin GVIA abolished the release of the neurotransmitter ATP evoked by trains of low-frequency stimuli. However, in the presence of high concentrations of the blocker, a 'residual release' persisted at higher frequencies. 3. Residual release was dependent on calcium entry through a pharmacologically distinct voltage-dependent calcium channel. 4. Residual release was inhibited by ryanodine in a use- and time-dependent manner and this inhibitory effect was potentiated by caffeine. The inhibitory effect of ryanodine on residual release was reversed by 4-aminopyridine. 5. These findings indicate that calcium-induced calcium released from intraneuronal stores plays an important role in action potential-evoked neurotransmitter release mechanisms in postganglionic sympathetic nerve terminals.