Ghrelin, a recently identified endogenous ligand for the growth hormone secretagogue (GHS) receptor, induces growth hormone (GH) secretion following systemic administration. We sought to determine whether systemic administration of ghrelin activates cells in the hypothalamic arcuate nucleus by examining the distribution of cells expressing Fos and Egr-1 proteins. In normally fed rats, both ghrelin and GHRP-6 (a synthetic GHS) significantly increased the number of cells expressing Fos and Egr-1 in the arcuate nucleus. The effects of ghrelin and GHRP-6 to induce Fos or Egr-1 protein expression was significantly greater in fasted than in fed rats. Thus, we show that (i) ghrelin is a centrally active peptide; (ii) it acts in a similar manner to synthetic GHS; and (iii) its central actions are increased in fasting, presumably reflecting physiological changes that accompany altered food intake and/or nutritional state.