In a neural cell line, the secretion of excitatory amino acids in response to a depolarizing stimulus is potentiated by the addition of serotonin. The duration of this potentiation is dependent on the strength of the stimulus. Persistent secretory potentiation induced by a strong stimulus requires the activation of both serotonin and NMDA receptors. Inhibiting the NMDA receptor during serotonin presentation prevented the induction of potentiation. The temporal characteristic of the potentiation is correlated with the elevation of cAMP levels. Serotonin exposure while inhibiting NMDA receptors results in a transient elevation of cAMP levels, whereas coactivation with NMDA and serotonin results in a persistent elevation of cAMP. Thus, it is possible to obtain potentiation of secretion in a single cell either transiently or persistently. The timing of potentiated responses in this system is of the same magnitude as that in similar systems used as models for short-term and long-term memory.