A common observation in studies of neuronal structure is that axons differ in the size of their synaptic boutons. The significance of this size variation is unclear, in part because we do not know how the size of synaptic boutons is related to their internal organization. The present study has addressed this issue by using three-dimensional reconstruction of serial thin sections to examine the ultrastructure of synaptic boutons that vary in size. Our observations are based on complete or near-complete reconstructions of 53 synaptic boutons contacting large neurons in the ventromedial gray matter of the upper cervical spinal cord (probable neck motor neurons). We characterized bouton size in terms of volume and total area of membrane apposed to the motor neuron surface (apposition area). Boutons vary in apposition area by a factor of 40, and there is a significant positive correlation between our two measures of bouton size. In addition, bouton size is systematically related to four ultrastructural variables: 1) total active zone area, 2) number of active zones, 3) individual active zone area, and 4) number of synaptic vesicles. The correlations between these variables and both of our measures of bouton size are positive and significant. These data suggest that bouton size may be an index of ultrastructural features that are thought to influence transmitter storage and release.