Synaptic depression that is induced by electrical stimulation of the glutamatergic neuromuscular junction (NMJ) of the crayfish can be offset by recruitment of vesicles from a presynaptic reserve pool. This recruitment occurs following treatment of the NMJ with serotonin (5-HT), which results in a delay in the onset of synaptic depression induced by high frequency stimulation. The results of this study demonstrate that the releasable vesicles are insufficiently replenished during high frequency stimulation and that the readily releasable pool of vesicles (RRP) can be enhanced by the reserve pool (RP) in the presence of 5-HT. Anatomical visualization of vesicular pools by transmission electron microscopy after depression or during 5-HT treatment showed no differences in the number of docked and RRP vesicles. We propose that the RRP vesicles can recycle empty and that a role for 5-HT might be to induce a rapid enhancement of synaptic transmission during synaptic fatigue