Electrical stimulation of the prefrontal cortex in anaesthetised, paralysed rats evokes transient hypotension. In this study we have endeavoured to determine whether this evoked response is mediated by the spinal cord-projecting vasomotor neurones of the rostroventrolateral medulla (RVL). The responses of RVL-spinal vasomotor neurones to electrical stimulation of the prefrontal cortex caused a period of inhibition of the neuronal activity in the majority of cases (11 out of 13 neurones tested, 85%) and a short period of excitation in the remaining 2 neurones (15%). The prefrontal cortex-evoked inhibition of RVL-spinal vasomotor neurones was eliminated by iontophoretic application of bicuculline, a GABAa receptor antagonist, to the RVL-spinal vasomotor neurones. Microinjection of 50 nl of bicuculline methiodide into the same area of the RVL where the neurones have been identified converted the prefrontal-evoked hypotension into a vasopressor response. These findings indicate that the hypotension evoked by stimulating the prefrontal cortex is mediated by GABAergic inhibition of the RVL-spinal vasomotor neurones.