We have investigated the impact of stochastic transmission on the input-output relations of neurons in hippocampal slices. A synaptic input that fires a cell has a significant trial-to-trial variability in amplitude, reflecting the probabilistic release of transmitter. By measuring miniature excitatory postsynaptic currents, we estimate that synchronous release of a few vesicles can fire a CA1 cell. The firing threshold and variability can be physiologically modulated. Different cell types have distinct firing thresholds and variabilities. Long-term potentiation (LTP) decreases trial-to-trial variability. If after LTP, the stimulus is reduced to produce a threshold response, the variability returns to that observed before LTP. Thus, for a threshold input, the trial-to-trial variability is maintained with LTP. This may be important for the proper functioning of a plastic nervous system.