During the aging process of mammals first a phase of obesity and increased adiposity is observed in middle-aged subjects, then anorexia and loss of body weight (sarcopenia) at old age. A possible age-dependence of the anorexigenic alpha-melanocyte-stimulating-hormone (alpha-MSH) in these regulatory changes was studied. Male Wistar rats aged 6-8 weeks (juvenile), 3-4 months (young adult), 6 and 12 months (middle-aged), and 24-26 months (old) were equipped with chronic cannula to the lateral cerebral ventricle. The effect of 5 microg alpha-MSH injected through the cannula was analyzed on food intake evoked by 24-h food deprivation. Juvenile rats seemed almost resistant to alpha-MSH (21.9% suppression). In young adults alpha-MSH suppressed food intake by 68.7%. However, the alpha-MSH-induced anorexia was significantly less pronounced in middle-aged (55.7% or 26.4% in rats aged 6 or 12 months, respectively), and much more pronounced (73.3%) in old rats. The adiposity (judged by the relative amount of perirenal fat) increased until middle-age, but did not change between middle-age and old-age. It is concluded that changes in alpha-MSH responsiveness possibly contribute to both the age-related obesity in middle-aged rats and to the anorexia of old ones: first the adiposity then the age may be the important factor.