We followed-up, from pregnancy to birth, a group of newborns both IUGR and AGA and we aimed at establishing placental biochemical determinants of birth weight and length. Insulin, total and activated insulin receptor contents (IR), cortisol and IL-6 placental concentrations were assayed in 23 IUGR and 37 AGA subjects at birth, and a multiple regression model was designed and applied to assess the significant biochemical determinants of birth size. IL-6 and activated insulin receptor content were significantly increased in IUGR, whereas insulin, total insulin receptor content, and cortisol placental concentrations were similar in IUGR and AGA. Placental cortisol concentration was found to be significantly and negatively related with both birth length (0.778, P<0.001) and weight (0.508, P<0.008). A negative effect of IL-6 placental concentration was found on birth length (P<0.002). For the first time we provide evidence of a negative association of placental cortisol and IL-6 concentrations on birth size.