Using whole cell recording from CA1 hippocampal pyramidal neurons in slices, we examined the progressive decrease of N-methyl-D-aspartate receptor-mediated synaptic responses in the presence of the open-channel blocker MK-801. Previous studies analyzing this decrease have proposed that hippocampal synapses fall into two distinct classes of release probabilities, whereas studies based on other methods indicate a broad distribution of synaptic reliabilities exists. Here we derive the theoretical relationship between the MK-801-mediated decrease in excitatory postsynaptic current amplitudes and the underlying distribution of synaptic reliabilities. We find that the MK-801 data are consistent with a continuous distribution of synaptic reliabilities, in agreement with studies examining individual synapses. In addition, changes in the MK-801-mediated decrease in response size as a consequence of altering release probability are consistent with this continuous distribution of synaptic reliabilities.