Salusin-β is an endogenous parasympathomimetic peptide, predominantly localized to the hypothalamus and posterior pituitary. Subcutaneously administered salusin-β (50 nmol/mouse) significantly increased water intake but did not affect locomotor activity or food intake. The salusin-β-induced increase in water intake was completely abrogated by pretreatment with muscarinic antagonist, atropine sulphate. In contrast, intracerebroventricular injection of salusin-β, at lower doses (10-100 fmol/mouse) caused a long-lasting decrease in water intake and locomotor activity throughout the entire dark phase of the diurnal cycle. Pre-injection of intracerebroventricular anti-salusin-β IgG completely abrogated the central salusin-β mediated suppression of water intake and locomotor activity. These results demonstrate contrasting actions of salusin-β in the control of water intake via the central and peripheral systems and highlight it as a potent endogenous antidipsogenic neuropeptide.