Phrenic motoneurons (PMNs) receive intermittently glutaminergic inspiratory drives and GABAergic inhibition in adult mammals. Since gamma-amino-butyric acid (GABA) might act as an excitatory amino acid in early stages of development, we here investigated if GABA(A) receptors inhibit PMNs in neonates. Using in vitro neonatal rat brainstem-spinal cord preparation, local application of GABA and muscimol (a GABA(A) receptor agonist) to the vicinity of PMNs consistently reduced the inspiratory activity of C4 ventral roots. Under whole-cell patch-clamp conditions and in the presence of 0.5 microM TTX to block synaptic transmission, muscimol (10 microM) decreased whole-cell input resistance, and surprisingly, when PMNs were voltage-clamped at their resting membrane potential, muscimol induced depolarizing-inward, rather than hyperpolarizing-outward membrane current. Our findings indicate that GABA(A) receptors mediate a depolarizing blockade of the glutaminergic excitatory inputs to neonatal rat PMNs.