The spinal trigeminal nucleus is involved in orofacial sensory transmission. Cholecystokinin octapeptide has been identified in axons in this nucleus and appears to play a role in the transmission of orofacial sensation from the trigeminal ganglia to the spinal trigeminal nucleus. Although cholecystokinin has been reported in axonal processes within the spinal trigeminal nucleus at the light microscopic level, nothing is known about the synaptic relationships of these cholecystokinin axons. The goals of this study were to quantitatively determine the volume fraction of cholecystokinin-like immunoreactive cell bodies and fibers in the three subnuclei of the spinal trigeminal nucleus, to provide the first ultrastructural description of cholecystokinin-like immunoreactive processes within these subnuclei and to analyse the synaptic relationships of cholecystokinin-like immunoreactive processes within the spinal trigeminal nucleus neuropil. Cholecystokinin-like immunoreactivity was localized by the peroxidase-antiperoxidase method or the peroxidase labeled, avidin-biotin technique and quantified at the light microscopic level by point counting. Immunoreactive fibers were present in all three subnuclei, but the greatest volume fraction of immunoreactive axons was obtained in laminae I and II of the nucleus caudalis. No immunoreactive cell bodies were evident in any of the subnuclei. The majority of immunoreactive profiles in all three subnuclei were identified ultrastructurally as axon terminals that contained both small and medium sized agranular vesicles and infrequently, large dense core vesicles. These immunoreactive terminals were usually found in close contact with non-immunoreactive dendrites with which they were observed to form asymmetric synapses. Immunoreactive terminals were occasionally observed to contact the cell bodies of large non-immunoreactive neurons on the border of laminae I and II in the nucleus caudalis. These results indicate that cholecystokinin-like immunoreactive processes are present throughout the spinal trigeminal nucleus and in nucleus caudalis show a distribution similar to that reported for the spinal cord dorsal horn. Immunoreactive axons make synaptic contact with both the dendrites and perikarya of spinal trigeminal nucleus neurons. No axoaxonic synapses were observed. These findings suggest that cholecystokinin plays an important role in spinal trigeminal nucleus function. The possible colocalization of cholecystokinin and substance P in the spinal trigeminal nucleus and the possible role of cholecystokinin in attenuating the action of opioids in the spinal trigeminal nucleus are also discussed.