Growth hormone secretagogues (GHS) administered systemically selectively induce growth hormone (GH) release from the pituitary and the expression of Fos protein in arcuate nucleus neurons. Both the control of GH release and the expression of the GHS receptor in the arcuate nucleus are thought to be regulated, at least in part, by the negative feedback actions of GH. In this study, we utilized the immunocytochemical detection of Fos protein to examine the effects of morphine- and GH-releasing hormone (GHRH)-induced GH release on the activation of arcuate nucleus neurons following GHS administration. Given alone, two structurally different GHS induced significant amounts of Fos-LI in the arcuate nucleus of male rats, suggesting activation of cells in this region. Prior administration of morphine or GHRH significantly reduced the number of Fos-positive cells in the arcuate nucleus of rats injected with either GHS, although when given together, morphine and GHRH did not produce a greater reduction in Fos expression than when given alone. In no case was there a complete reduction in Fos expression, indicating that some arcuate nucleus neurons are not subject to the feedback effects of endogenous GH. These results provide evidence that, in the male rat, GH can feedback to the hypothalamus, altering the responsiveness of neurons involved in the central response to GHS.