Agouti-related peptide (AgRP), the endogenous antagonist to the melanocortin 3 and 4 receptors, elicits robust hyperphagia and weight gain in rodents when administered directly into the central nervous system. The relative influence of AgRP to cause weight gain in rodents partially depends on the activity level of the melanocortin agonist-producing pro-opiomelanocortin (POMC) neurons. Both POMC and AgRP neurons within the arcuate nucleus receive energy storage information from circulating peripheral signals such as leptin and insulin. Another modulator of AgRP activity includes the cell surface molecule syndecan-3. Because leptin and insulin affect food intake in a sexually dimorphic way in rodents and syndecan-3 deficient mice regulate adiposity levels through distinct physiological mechanisms, we hypothesized that AgRP-induced weight gain would also be sexually dimorphic in rats. In the present study the behavioral and physiological effects of centrally-administered AgRP in male and female were investigated. Male rats displayed 5 days (p<0.0001) of hyperphagia compared to 3 days (p<0.05) in female rats following a single injection of 1 nmol AgRP. However, one week after the injection both male and female rats gained the same percent body weight (6%). Interestingly, female rats show a greater reduction in energy expenditure (VO₂) following AgRP compared to male rats (p<0.05). Removal of the gonads did not alter cumulative food intake in male or female rats but did attenuate the dramatic reduction in VO₂ exhibited by females. Both intact and gonadectomized rats demonstrated significantly increased respiratory quotient supporting the anabolic action of AgRP (p<0.01). These findings are novel in that they reveal sex-specific underlying physiology used to achieve weight gain following central AgRP in rats.