The adipose tissue hormone leptin, which is secreted to the general circulation and transported into the brain in a facilitated manner, possibly acts via hypothalamic neurones to reduce food intake and increase energy expenditure. To evaluate the involvement of importance of the arcuate nucleus in leptin induced anorexia, groups of rats treated neonatally with monosodium-glutamate (MSG; arcuate lesioned) and littermate controls were injected centrally with 5 microg recombinant leptin or saline daily for three consecutive days. Leptin significantly inhibited food intake and caused weight-loss in non-MSG rats (-14.5+/-3.0 g vs. 10.2+/-4.3 g; mean +/-s.e.m.; leptin vs. vehicle) whereas MSG-treated rats were unresponsive to leptin treatment (5.0+/-2.2 g vs. 0.8+/-3.8 g; leptin vs. vehicle). The present data indicate that an intact arcuate nucleus is necessary for leptins actions on food intake and body weight.