Rats pretrained to walk a narrow balance beam received unilateral sensorimotor cortex lesions, resulting in a contralateral transient paresis that lasted 14 days. In a dose-dependent manner, a single injection of the antidepressant trazodone given 24 hours after injury transiently slowed motor recovery compared with injured controls. After final recovery level of motor function, a reinjection of trazodone reinstated the hemiparesis for up to 6 hours. In other animals, a single injection of the antidepressant desipramine significantly facilitated motor performance when compared with injured controls. Desipramine had no deleterious motor effect when administered to animals that had recovered on the beam-walking task. These findings would suggest that the predominately noradrenergic neurotransmitter effects of desipramine may facilitate, and those of the predominately serotonergic trazodone may hinder, the recovery of locomotor performance after cortical injury in rats. Further studies appear indicated, including applying these findings to the clinical setting.