We report on factors affecting the spontaneous firing pattern of the identified serotonin-containing Retzius neurons of the medicinal leech. Increased firing activity induced by intracellular current injection is followed by a 'post-stimulus-depression' (PSD) without spiking for up to 23 s. PSD duration depends both on the duration and the amplitude of the injected current and correlates inversely with the spontaneous spiking activity. In contrast to serotonin-containing neurons in mammals, serotonin release from the Retzius cells presumably does not mediate the observed spike suppression in a self-inhibitory manner since robust PSD persists after synaptic isolation. Moreover, single additional spikes elicited at specific delays after spontaneously occurring action potentials are sufficient to significantly alter the firing pattern. Since sub-threshold current injections do not affect the ongoing spiking pattern and PSD persists in synaptically isolated preparations our data suggest that PSD reflects an endogenous and 'spike-dependent' mechanism controlling the spiking activity of Retzius cells in a use-dependent way.