Cigarette-smoking during pregnancy is associated with a variety of fetal risks including intrauterine growth retardation. We describe the effect of chronic exposure of pregnant women to nicotine on umbilical cord concentrations of IGF-I and IGF-Binding Protein 3 (IGFBP-3). We studied IGF-I and IGFBP-3 concentrations in 10 smoking (>15 cigarettes daily for > two months of gestation) and 9 non-smoking and not passively to cigarette-smoke exposed mothers (median ages 27 and 28 years, respectively), who -after an uneventful pregnancy- gave birth to normal term babies. For the assessment of nicotine exposure we determined concentrations of nicotine metabolite cotinine by ELISA in maternal hair obtained at delivery. Maternal hair cotinine content was 10-fold higher in the nicotine-exposed group than in non-nicotine exposed(4.51 ± 1.72, range 2.41 - 7.98, versus 0.45 ± 0.31, range 0.1 - 0.99, ng/mg hair; p < 0.0003). Cord blood concentrations of IGF-I were 3-fold lower (p < 0.026) in the smoking group (2.3 ± 1.6, range 0.7- 5.6 nM) than in the nonsmoking group (7.0 ± 3.5, range 3.0 - 11.1 nM). IGFBP-3 levels were not different (63.9 ± 17.7, range 41.8 - 94.1 nM) versus (66.0 ± 23.3, range 37.8 - 97.1 nM) in the two groups. These findings indicate, that IGF-I concentrations in cord blood of babies born to smoking mothers are significantly lower. Since IGFBP-3 concentrations were similar for both groups, the decrease in IGF-I concentrations in the smoking group is unlikely due to an increased binding to its plasma-binding protein but rather to decreased production or enhanced degradation of IGF-I, possibly influenced by high levels of nicotine. Growth retardation in fetuses of smoking mothers could be related to the effect of nicotine on generation and/or processing of IGF-I.