Orexinergic and histaminergic neurons in the posterior hypothalamus are involved in the control of arousal. Extracellular levels of acid and CO₂ are fundamental physicochemical signals controlling breathing and wakefulness. Acidification excites orexinergic neurons in a manner resembling the action on chemosensory neurons in the brain stem but effects on histaminergic neurons, whose dendrites are often located conspicuously close to the brain surface, are unknown. We found that acidification within the physiological range (pH from 7.4 to 7.0) excites histaminergic neurons to 150% of control firing. The magnitude of this excitation is similar to the action of ammonium chloride (5mM), which induces intracellular acidification. Acid-sensing ion channels (ASIC) can be gated by NH₄⁺ (Pidoplichko and Dani, 2006, PNAS). Mechanisms of chemosensing by histaminergic neurons are investigated now using patch-clamp recordings from rat brain slices and single cell RT-PCR. Histaminergic neurons express variable combinations of 4 known types of ASIC according to a pharmacological analysis of pH-induced current. In addition, transcripts of the vanilloid receptor 1 (TRPV1), which responds to heat, capsaicin and protons, were detected in histaminergic neurons. Blockers of TRPV1, ASIC, Na⁺/K⁺ ATPase or type 1 metabotropic glutamate receptors prevented pH-induced excitation. These results are relevant for the understanding of neuronal mechanisms controlling H⁺/CO₂-induced arousal, which are compromised in hepatic encephalopathy.