The caudal ventral respiratory column (cVRC) contains premotor expiratory neurons that play an important role in cough-related expiratory activity of chest wall and abdominal muscles. Microinjection of D,L-homocysteic acid (DLH) was used to test the hypothesis that local activation of cVRC neurons can suppress the cough reflex. DLH (20-50 mM, 10-30 nl) was injected into the region of cVRC in 9 anesthetized spontaneously breathing cats. Repetitive coughing was elicited by mechanical stimulation of the intrathoracic airways. Electromyograms (EMG) were recorded bilaterally from inspiratory parasternal and expiratory transversus abdominis (ABD) and unilaterally from laryngeal posterior cricoarytenoid and thyroarytenoid muscles. Unilateral microinjection of DLH (1-1.5 nmol) elicited bilateral increases in tonic and phasic respiratory ABD EMG activity, altered the respiratory pattern, and laryngeal motor activities. However, DLH also decreased cough frequency by 51±7% compared to control (p<0.001) and the amplitude of the contralateral (-35±3%, p<0.001) and ipsilateral (-34±5%, p<0.001) ABD EMGs during post injection coughs compared to control. The cough alterations were much less pronounced after microinjection of a lower dose of DLH (0.34-0.8 nmol). No cough depression was observed after microinjections of vehicle. These results suggest that an endogenous cough suppressant neuronal network in the region of the cVRC may exist and this network may be involved in the control of cough reflex excitability.