Rhythmically active medullary slice preparations isolated from neonatal rats (postnatal days 0-3, P0-P3) were used to study the modulation of respiraory rhythmogenesis and hypoglossal (XII) nerve discharge by serotonin (5-hydroxytryptamine, 5-HT) and noradrenaline (NA). 5-HT, NA and their respective receptor agonists and antagonists were applied either to the bathing medium or focally via pressure injection into regions encompassing the pre-Botzinger complex or XII motoneurons. The effects of endogenously released 5-HT were also studied by chemical stimulation of neurons within the raphe obscurus. The frequency of respiratory burst discharge was increased when 5-HT was applied: (1) to the bathing medium (37+/-16%; 30 "mu"M; P < 0.05); (2) via pressure injection into the region of the pre-Botzinger complex (22 +/- 14%; < 25 pmol; P < 0. 05); or (3) endogenously released in response to activation of neurons within the raphe obscurus via pressure injection of (R,S)- "alpha"-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA, 34 +/- 15%; P < 0.05) or 5-HT (33 +/- 5%; P < 0. 05). All of these effects were antagonized by bath application of methysergide (30-40 "mu"M). NA caused a reduction of respiratory burst frequency when applied to the bathing medium (40 +/- 15%; 100 "mu"M; P < 0.05) or when pressure injected into the region of the pre-Botzinger complex (22 +/- 11%; < 25 pmol; P < 0.05). These effects were blocked by the bath application of the "alpha"2-receptor antagonist idazoxan (2 "mu"M). 5-HT and NA both caused an augmentation of tonic discharge of XII nerves when applied either to the bathing medium or via pressure injection into the XII motoneuron pool. The 5-HT-induced XII nerve tonic discharge was mimicked by the 5-HT2 receptor agonist R(-)2-(2, 5-dimethoxy-4-iodophenyl) (DOI.HCl, 5 "mu"M) and blocked by the 5-HT2 receptor antagonist ketanserine tartrate (30-40 "mu"M). The NA-induced XII nerve tonic discharge was mimicked by the "alpha"1-receptor agonist phenylephrine HCl (500 nM) and blocked by the "alpha"1-receptor antagonist prozasin HCl (1 "mu"M).