Norepinephrine (NE) has powerful, and diverse modulatory effects on XII motoneuron activity, which is important in maintaining airway patency. The objective was to test two hypotheses that ₂ adrenoceptor- mediated, presynaptic inhibition of glutamatergic inspiratory drive (58), and postsynaptic inhibition of the hyperpolarization-activated inward current, I_h (50) modulate XII inspiratory activity. Nerve and whole-cell recordings were applied to rhythmic medullary slice preparations from neonatal rats (P0-P4) to monitor XII inspiratory burst amplitude and motoneuron properties. Application of an ₂ receptor agonist (clonidine, 1 mM) to the XII nucleus reduced inspiratory burst amplitude to 71±3% of control, but had no effect on inspiratory synaptic currents. It also reduced the I_h current by ~40%, but an I_h current blocker (ZD7288), at concentrations that blocked ~80% of I_h, had no effect on inspiratory burst amplitude. The clonidine inhibition was unaffected by the GABA_A antagonist, (+)bicuculline, but attenuated by the ₂ antagonist, rauwolscine, and the imidazoline I₁ antagonist, efaroxan. The I₁ agonist, rilmenidine, but not the ₂ agonist, UK14304, inhibited XII output. Clonidine also reduced action potential amplitude or impaired repetitive firing. While a contribution from ₂, and in particular I₁, receptors remains possible, results demonstrate that: i) noradrenergic modulation of XII inspiratory activity is unlikely to involve ₂ receptor-mediated presynaptic inhibition of glutamate release or modulation of I_h; ii), inhibition of repetitive firing is a major factor underlying the inhibition of XII output by clonidine; and iii) I_h is present in neonatal XII motoneurons but does not contribute to shaping their inspiratory activity.