Abstract: Abstract Pyramidal neurons of the rat medial prefrontal cortex have been shown to react to chronic stress by retracting their apical dendrites and by spine loss. We extended these findings by focusing on the basilar dendritic tree of layer III pyramidal neurons in both hemispheres of the rat prelimbic cortex. Animals were subjected to daily restraint stress for 1 week (6 h/day), during either the resting or the activity period. The morphology of basilar dendrites and spines of Golgi–Cox-stained neurons in the left and right hemispheres was digitally reconstructed and analyzed. We observed the following: (i) there was an inherent hemispheric asymmetry in control rats during the resting period: the number of spines on proximal dendrites was higher in the left than in the right hemisphere; (ii) basal dendrites in controls displayed a diurnal variation: there was more dendritic material during the resting period than in the activity period; (iii) chronic stress reduced the length of basal dendrites in only the right prelimbic cortex; (iv) chronic stress reduced spine density on proximal basal dendrites; (v) restraint stress during the activity period had more pronounced effects on the physiological stress parameters than restraint stress during the resting period. Our results show dynamic hemisphere-dependent structural changes in pyramidal neurons of the rat prelimbic cortex that are tightly linked to periods of resting and activity. These morphological alterations reflect the capacity of the neurons to react to external stimuli and mirror presumptive changes in neuronal communication.