The present study was conducted to evaluate the effects of neonatal treatment of male rats with monosodium-L-glutamate (MSG) on levels of immunoreactive somatostatin (IRS) in specific regions of the gastroenteropancreatic (GEP) system, in discrete hypothalamic areas, and in peripheral blood. In two identical experiments, IRS concentrations measured in the arcuate nucleus and median eminence of adult, MSG-treated rats were significantly reduced in comparison to IRS levels measured in control littermates. Levels of IRS in the preoptic-periventricular nucleus were significantly reduced only in one experiment. In contrast, neonatal MSG treatment resulted in a twofold increase of IRS levels in the pancreas and antral region of the stomach. Peripheral plasma IRS concentrations were significantly elevated in MSG-treated rats only in one experiment. Since MSG-treated rats have a deficiency in growth hormone (GH) secretion, an additional experiment was performed to determine if GH replacement therapy could reverse some or all of the changes in IRS concentrations induced by MSG treatment. With the exception of a further increase in antral IRS levels, replacement with rGH failed to restore IRS levels in other tissues or plasma of MSG rats to levels measured in control rats. These results show that neonatal MSG treatment not only affects IRS levels in the hypothalamus and blood as previously reported, but in parts of the GEP system as well. Further, effects on hypothalamic IRS levels are opposite to those on GEP IRS levels. The significance of these findings may relate to the altered metabolic state of these animals as a consequence of perturbations in the secretion of other hormones from the hypothalamus, anterior pituitary gland, and possibly the GEP system.