Leptin, the secreted and translated product of the ob gene, acts upon the adult hypothalamus and decreases appetite and body weight gain. While neonatal rat and mouse adipocytic leptin mRNA and circulating peptide have been detected (FASB J 11:382-387, 1997; BBRC 238:44-47, 1997), and neonatal rat hypothalamic leptin receptors characterized (Ped Res 1998), the biological significance of leptin in the newborn remains unknown. To address this issue, 2 to 8 day old rats received intracerebroventricularly 0.5 μg (n=3) and 1μg (n=3) of murine leptin or vehicle (n=6) on a daily basis. In comparison to the vehicle group, a ≈27% body weight loss was noted in the 0.5 μg and 1 μg leptin groups by day 7 (leptin=8±0.5g vs vehicle=10.9±0.7g; p < 0.05). This weight loss persisted through day 9 (leptin=11.1±0.1g vs vehicle=15.5±0.3g; p < 0.05), declined to ≈11% by day 16 (leptin= 30.1±3g vs vehicle=36.9±0.7g; p< 0.05), and was no different at day 24. Though no change in plasma leptin or glucose concentrations was noted throughout, an increase in plasma insulin was observed only at day 3 in the 1μg leptin group (4.9±0.1 vs the vehicle group= 2.9±0.8 ng/ml; p < 0.05). In an attempt to determine the central mechanism(s) by which leptin induced this neonatal body weight loss, semi-quantitation of paraventricular neuropeptide Y immunoreactivity(NPY; aerence in NPY amounts was detected at 3d which is 24 hours following initiation of leptin administration. This is in contrast to our previous investigations where intracerebroventricular NPY led to biological changes within 24 hours (Varma et al Ped Res 41:1441, 1997). Studies assessing hypothalamic NPY levels between 7 to 24 days are in progress. We conclude that 1] exogenous intracerebroventricular leptin administration reduces body weight during the suckling phase, and 2] the anorexic/catabolic effect is observed 5 days after initiation of intracerebroventricular leptin injections. We speculate that the hypothalamic mechanism(s) for this biological response may include reduction in NPY synthesis/levels at later ages (7 to 24 d), or even perturbations in other anorexic neuro peptides(corticotropin-releasing hormone, proopiomelanocortin).