Several lines of evidence suggest that brain histamine may be involved in the central control of food intake. The effect of histamine on feeding is mediated through three kinds of receptors (H1, H2, and H3). The present study was designed to investigate the effect of intracerebroventricular injection of histamine, promethazine (H1 antagonist) and ranitidine (H2 antagonist) on food intake of freely feeding and food-deprived (for 16 h) rabbits. For intracerebroventricular injections, a 23-gauge, 18 mm long stainless steel guide cannula was surgically implanted into the left lateral ventricle of brain. Ten days after cannulation, intracerebroventricular injection of normal saline (control), histamine (25, 50, 100, and 200 ?g/rabbit) promethazine and ranitidine at the same doses of 100 and 200 ?g/rabbit alone or before injection of histamine were performed using a 25?l Hamilton’s syringe. Food intake was measured at 1, 2, 3, 6 and 24 h after injections. Data were analyzed by factorial ANOVA and Duncan test. The results showed that 16 h food deprivation increases 1, 2 and 3 h food intake. The 6 and 24 h food intake was not affected by food deprivation. In freely feeding rabbits, histamine (25 ?g) had no effect, but at doses of 50, 100 and 200 ?g decreased food intake. Promethazine (100 and 200 ?g) alone increased food intake, and pretreatment with promethazine prevented the histamine-induced anorexia. Ranitidin alone had no effect, and pretreatment with ranitidine did not inhibit the effect of histamine. In the 16 h food-deprived rabbits, histamine (25 and 50 ?g) had no effect, but histamine (100 and 200 ?g) decreased food intake. Promethazine and ranitidine alone had no effects. Pretreatment with promethazine blocked the histamine-induced anorexia of histamine on food intake. Based on the findings of the present study it is concluded that the activation of brain histamine system produces anorexia in the freely feeding and food-deprived rabbits. The anorectic effect of histamine is mediated through its central H1, but not H2 receptors.