Male and female rats fed on a restricted feeding (RF) schedule of 4 weeks to produce 20-25% reduction in body weight, were killed before (starved) and after (fed) the presentation of food to compare 5-hydroxytryptamine (5-HT) metabolism in the hypothalamus with respective freely feeding (FF) controls and to monitor sex differences in RF-induced changes of 5-HT. RF decreased plasma tryptophan concentration in RF starved and RF fed females and also in RF starved males. In the hypothalamus tryptophan levels decreased in RF starved and RF fed female rats and RF fed males. 5-HT decreased in both RF starved and RF fed male and female rats and the decreases were comparable in the two sexes. 5-hydroxyindoleacetic acid (5-HIAA), a major metabolite of 5-HT was not affected. Food restriction decreased 5-HT concentration in the rest of the brain of male but not female rats. Possible implications of the findings in the pathogenesis of food restriction/starvation related disease anorexia nervosa and its greater occurrence in women than men is discussed.