Objective: Nitric oxide (NO) is a potent vasodilator released by endothelial cells that plays an important role in modulating maternal and fetal vascular tone in normal pregnancy. Lower plasma levels of vitamins may result in hyperhomocysteinemia, a known risk factor in pregnancy. The aim of this study was to investigate whether there are alterations in the serum levels of total homocysteine (tHcy), folate, vitamin B-12, and total nitrite, as an index of NO, in smoking as compared with age-matched nonsmoking pregnant women. Methods: Thirty-three women (19 smoking and 14 nonsmoking) between 16 and 22 weeks of their gestation were included in this study. The serum tHcy levels were analyzed by using an enzyme-linked immunosorbent assay kit. Vitamin B12 and folate values were measured by means of DPC kits. Total nitrite was measured by Griess reaction as an index of endogenous NO production. Results: The serum tHcy concentrations were significantly increased in smoking as compared with nonsmoking pregnant women (p<0.001). The folate and vitamin B-12 concentrations were lower in smoking than in nonsmoking pregnant women, but only the differences in folate concentrations were statistically significant (p<0.001). The tHcy concentrations showed a significant negative correlation with folate in the smoking pregnant women. The serum total nitrite concentrations were lower in smoking than in nonsmoking pregnant women (p<0.05). In addition, the serum nitrite levels in smoking pregnant women had significant negative correlations with tHcy and positive correlations with folate and vitamin B-12 levels. Conclusions: In the light of our findings, we propose that smoking might enhance the vasoconstrictor capacity in pregnant women by increased tHcy concentrations and by a simultaneous decrease in the production of NO which is a vasodilator compound. Copyright (C) 2004 S. Karger AG, Basel.