We have investigated the action of ciguatoxin (CTX) in the mouse following i.p. administration. CTX (0.5 mouse units) induced a rapid (10-20 min) decrease in body temperature that persisted for several hours. This corresponded closely with a neuroexcitatory action of ciguatoxin on c-fos mRNA in the brain. We identified the neuronal pathways activated by CTX action in the mouse brain by immunostaining of c-fos translational product, a biomarker for neuroexcitability. c-fos-like immunoreactivity was prominent in the hypothalamus, including the medial preoptic and supraoptic nuclei. Immunostaining was also evident in certain regions of the brain stem, including the locus coeruleus, dorsolateral parabranchial nucleus, area postrema and the nucleus of the solitary tract. These studies indicate that CTX has neuroexcitatory actions on brain stem regions receiving vagal afferents and ascending pathways associated with visceral and thermoregulatory responses.