We have previously shown that the caudal nucleus tractus solitarii is a site of action of some antitussive drugs and that the caudal ventral respiratory group (cVRG) has a crucial role in determining the cough motor pattern. These findings led us to suggest that the cVRG may also be a site of action of antitussive drugs. To address this issue, we investigated changes in baseline respiratory activity and cough responses to tracheobronchial mechanical stimulation following microinjections (30–50 nl) of some antitussive drugs into the cVRG of pentobarbitone anesthetized, spontaneously breathing rabbits. DAMGO and baclofen at the lower concentrations (0.5 and 0.1 mM, respectively) decreased cough number, peak abdominal activity, peak tracheal pressure, and increased cough-related total cycle duration (T_T). At the higher concentrations (5 and 1 mM, respectively), both drugs abolished the cough reflex. They also affected baseline respiratory activity. Both drugs reduced peak abdominal activity, while only DAMGO increased T_T. The neurokinin-1 (NK₁) receptor antagonist CP-99,994 (10 mM) decreased cough number, peak abdominal activity and peak tracheal pressure, without affecting baseline respiration. The NK₂ receptor antagonist MEN 10376 (5 mM) had no effect. The results suggest that several neural substrates involved in cough regulation may be sites of action of antitussive agents.