Intrapulmonary chemoreceptors (IPC) and extrapulmonary afferents (EPA) have been shown to interact in ventilatory control in the chicken. It is not clear, however, if all or only some of the EPA are involved in this interaction with IPC. We therefore designed this study to determine if afferents carried in the middle cardiac nerve (MCN) interact centrally with IPC. We anesthetized six cockerels with sodium pentobarbital (ca. 30 mg/kg), cannulated the cutaneous ulnar vein and carotid artery, opened the thorax, and unidirectionally ventilated each lung separately. The right, denervated lung was used to fix PaCO2 at the following levels: 89.5 +/- 1.1, 41.9 +/- 0.6, 35.9 +/- 0.8, and 23.6 +/- 0.5 Torr. At each PaCO2, we measured ventilatory and blood pressure responses while the left, non-perfused lung was ventilated with gases ranging from 70.2 to 15.7 Torr PCO2. We then cut the MCN and repeated the protocol. We found that MCN section increased the amplitude of sternal deflections (SD/SDmax) at all levels of intrapulmonary PCO2 and reduced the respiratory period (T/Tmax) at all but the highest level of intrapulmonary PCO2. Mean arterial pressure increased following MCN section, and this increase was independent of intrapulmonary PCO2. Multiple regression analyses of SD/SDmax revealed that MCN section reduced both arterial CO2 sensitivity and the interaction between EPA and IPC. These findings suggest that afferents carried in the MCN interact with IPC to reduce ventilatory amplitude during hypocapnia.