Recent ultrastructural descriptions of synaptic contacts suggest that potential synaptic efficacy may be directly correlated with bouton size. The characteristics of a synaptic bouton which presumably underlie its potential physiological strength (such as vesicle number, active zone number and area, and mitochondrial volume) are all linearly related to the volume of the bouton. Furthermore, at synapses which contact dendritic spines in both the hippocampus and cerebellum, the volume of the spine is linearly related to bouton volume. The existence of these scaling relationships has widespread implications for interpreting synaptic anatomy and variability, and for examining synaptic plasticity. We review evidence in support of the "ultrastructural size principle" outlined above and its potential generality.