Morphological plasticity occurs in the phrenic nucleus within hours following an ipsilateral C2 spinal cord hemisection. The plasticity has been associated with the unmasking of a latent respiratory pathway (the crossed phrenic pathway) which allows recovery of the hemidiaphragm paralyzed by the hemisection during a reflex known as the crossed phrenic phenomenon. This study tests if the plasticity is induced by the generalized effects of spinal cord trauma or the more specific effect of interrupting the main descending respiratory drive to phrenic motoneurons. Electron microscopic quantitative morphometric analysis of the phrenic nucleus neuropil was carried out on four Sprague-Dawley rats (200-250 g) sacrificed 4 h following unilateral reversible cold block of the descending bulbospinal respiratory drive at the second cervical segment of the spinal cord (C2). The data from four sham-operated control animals were compared with those of the experimental group. The following morphological alterations were documented in cold block animals compared to controls: (1) a significant increase in the number of multiple synapses (i.e., terminals with synaptic active zones contacting two or more postsynaptic profiles in the same plane of section), (2) a significant increase in the number of dendrodendritic appositions, and (3) a significant increase in the length of symmetric and asymmetric synaptic active zones. The above changes are similar to the changes induced in the phrenic nucleus following C2 hemisection. We conclude therefore, that injury to the spinal cord is not a requirement for this type of morphological plasticity in the phrenic nucleus, but rather the induced changes are activity-dependent and are likely caused by the interruption of the descending bulbospinal respiratory drive to the phrenic nucleus.