To identify sites of histaminergic modulation of food intake, histamine H1-receptor antagonist was microinfused into the rat hypothalamus, the ventromedial hypothalamus (VMH), the lateral hypothalamus (LHA), the paraventricular nucleus (PVN), the dorsomedial hypothalamus (DMH), or the preoptic anterior hypothalamus (POAH), during the early light period. Feeding, but not drinking, was elicited in 100% of the rats (P less than 0.01) that were bilaterally microinfused with 26 nmol chlorpheniramine into the VMH. Unilateral infusion into the VMH did not affect food intake at doses of 26 or 52 nmol. Feeding was also induced by bilateral microinfusion into the PVN, but only the 52 nmol dose was effective. Bilateral infusions into the LHA, the DMH or the POAH did not affect ingestive behavior. Feeding induced by an H1-antagonist was completely abolished in all 7 rats tested when endogenous neuronal histamine was decreased by pretreatment with alpha-fluoromethylhistidine (100 mg/kg). The findings suggest that H1-receptors in the VMH and the PVN, but not in the LHA, the DMH or the POAH, may be involved in histaminergic suppression of food intake.