Chronic intermittent hypoxia (CIH) produces expiratory-related sympatho-excitation in rats, which might be an important contributor to the development of neurogenic hypertension. We evaluated the role of sympatho-excitatory cathecolaminergic medullary C1 neurons in mediating the expiratory-related sympatho-excitation and hypertension in CIH rats. In awake and in situ perfused preparations of rat, C1 neurons were acutely silenced by application of the insect peptide allatostatin following cell-specific targeting with a lentiviral vector to express the inhibitory Drosophila allatostatin receptor in C1 neurons of control and CIH rats (10 days). In awake rats, inhibition of ~ 72% of the C1 neurons resulted in a profound fall in arterial pressure and heart rate that was similar in control (n=12) and CIH rats (n=12). However, CIH rats still presented high arterial pressure after C1 inhibition (p<0.05) when compared to control rats. In in situ, C1 neuron inhibition resulted in reversible reductions of firing frequency, perfusion pressure, and amplitude of inspiratory-related bursts of thoracic sympathetic nerve activity in control (n=7) and CIH (n=9) rats. We also documented that CIH- (n=9), acute hypoxia- (n=7) or CO2-induced expiratory-related sympatho-excitation (n=10) were not affected by C1 inhibition. These data confirm an important physiological role of C1 neurons in regulating sympathetic activity and arterial pressure, but apparently they are not involved in the expiratory-related sympatho-excitation that is characteristic of the hypertension evoked by CIH in rats.