Background: Prenatal L-NAME exposure results in fetal and placental growth retardation. Aim: To determine the effects of L-NAME treatment on specific organ growth,and further evaluate nitric oxide production. Methods: Timed-pregnant dams were randomly assigned to two prenatal treatment groups (1) water control (2) L-NAME, a nitric oxide synthase inhibitor, at a dose of 1 mg/ml in the drinking water for the last 7 prenatal days. At 21 days gestation, fetal and placental weights including fetal organ weights (brain, lungs, heart, liver and intestines) were determined. Nitric oxide production was measured by maternal urinary cGMP, ex vivo production of nitrite levels, iNOS gene expression and microelectrode electrochemical quantification of NO release in tissue explanst.Results: As seen previously, L-NAME treatment resulted in fetal and placental growth retardation. Fetal organ weights normalized for pup size were significantly increased for brain, heart, and intestine (p<0.05) and decreased in liver (p<0.05) in L-NAME treated pups. Paradoxically, administration of L-NAME increased nitric oxide production (p<0.05) in the maternal uterus and placenta determined by direct microelectrode measurement and confirmed by ex vivo synthesis of nitrite and urinary cGMP. However, iNOS gene expression was unaltered. Conclusions: Fetal growth retardation secondary to L-NAME treatment is asymmetric compared to controls. The effect of L-NAME is not due to a lack of nitric oxide release by the utero-placental unti, rather there is a paradoxical increase in NO release.