Whilst the early postnatal leptin peak (between postnatal day 8 and 21) in rodents that programs the balance of orexigenic and anorexigenic appetitive neuropeptides and influences future leptin sensitivity is firmly established, existence and timing of a leptin peak in precocial animals (sheep and primates including humans) has received less attention. We have demonstrated a neonatal leptin peak between day 4 and 9 in sheep. In obese sheep (OB) we showed that the neonatal leptin peak is eliminated in the first (F1) (Fig 1) and second generation (F2 – fed normal diet from weaning through gestation) offspring of OB ewes (Fig 1). Adult OBF1 and OBF2 offspring of OB mothers exhibited markedly increased appetites, glucose and insulin dysregulation, increased adiposity, and were hyperleptinemic compared to F1 and F2 offspring of control-fed F0 ewes. OBF1 lambs and their offspring OBF2 lambs show elevated plasma cortisol at birth compared with control F1 and F2 lambs (Fig 1B and D). Cortisol has important roles in prenatal regulation of cell proliferation and differentiation to mature fetal tissues in preparation for extra-uterine life. Cortisol Levels higher than appropriate for current maturation may cause premature adipocyte differentiation, altering timing of the neonatal leptin peak. This hypothesis is supported by our findings that offspring of ewes given exogenous glucocorticoids in late gestation exhibited elimination of the neonatal leptin peak as seen in OB offspring. Similarities and differences in maternal, fetal and perinatal life between rodents, sheep, nonhuman primates and man will be discussed.