Whole-cell patch recordings were made from immature (six- to 12-day-old) rat rostral ventrolateral medulla neurons in brainstem slices. GABA or the specific GABA B receptor agonist (−)baclofen (10–50 μM) by superfusion or by pressure ejection induced an outward current or a hyperpolarization, which persisted in a tetrodotoxin (0.3 μM)-containing Krebs' solution in nearly every cell tested. The GABA B receptor antagonists 2-hydroxy saclofen (50–200 μM) and CGP 35348 (50–200 μM) dose-dependently suppressed baclofen-currents. Baclofen-currents were suppressed by barium (1 mM) but not by tetraethylammonium (20 mM), low Ca 2+ (0.24 mM) solution or in a solution containing the Ca 2+ chelator BAPTA-AM (10 μM). The outward current had an estimated reversal potential of −98, −77 and −52 mV in 3.1, 7 and 15 mM [K +] o. Pre-incubation of slices with pertussis toxin (500 μg/ml for 5–7 h) or intracellular dialysis with GDP- β-S (500 μM) markedly reduced baclofen-currents. Baclofen in low concentrations (1–3 μM) that caused slight or no change of holding currents and of inward or outward currents induced by exogenously applied glutamate or glycine/GABA, decreased excitatory and inhibitory postsynaptic currents by an average of 86.5±4.3% and 78.4±2.7%. The GABA B antagonist CGP 35348 (100 μM) increased the excitatory postsynaptic currents by an average of 64%, without causing a significant change in holding currents in 10/18 cells tested. Our results indicate the presence of post- and presynaptic GABA B receptors in the rostral ventrolateral medulla neurons. Activation of postsynaptic GABA B receptors induces an outward K + current which is barium-sensitive, Ca 2+-independent and may be coupled to a pertussis-sensitive G-protein. Activation of presynaptic GABA B receptors attenuates excitatory or inhibitory synaptic transmission. More importantly, the observation that CGP 35348 enhanced excitatory synaptic currents implies a removal of tonic activation of presynaptic GABA B receptors by endogenously released GABA (disinhibition), supporting the hypothesis that these receptors may have a physiological role in regulating the input and output ratio in a subset of rostral ventrolateral medulla neurons in vivo.