Background.One of the possible mechanisms responsible for pre‐eclampsia is a loss of efficiency of the L‐arginine‐nitric oxide pathway with subsequent inactivation of the guanylyl cyclases of the vascular smooth muscle cells. As a result there should be a decrease in plasma cyclic 3′‐5′ guanosine monophosphate (cGMP) concentrations in pre‐eclampsia. We assessed the behavior of this nucleotid in the plasma of pre‐eclamptic women.Subjects and methods.Sixteen pre‐eclamptic women, 16 normotensive pregnant women matched for gestational age and six nonpregnant controls were investigated. Arterial blood pressure was recorded at inclusion time and then once a‐day until the fourth day after delivery concomitantly with the collection of blood samples for determining plasma cGMP, atrial natriuretic peptides (ANP). creatinine, uric acid and platelet counts. Also 24 h urines were simultaneously collected to calculate renal clearance of cGMP.Results.Before the initiation of antihypertensive treatment, plasma cGMP levels were significantly higher (p<0.01) in pre‐eclampsia women as compared both to pregnant normotensive controls and nonpregnant women (7.02±0.9 versus 4.8±0.76 versus 1.93±0.15 pmol‐ml−1, p<0.01). Under antihypertensive treatment, cGMP levels decreased significantly (p<0.05) to 5.48±0.9 pmol‐ml−1. The increase of plasma cGMP was associated with high ANP levels; the likelihood that a renal impairment could account for an increase in plasma cGMP was ruled out because the clearance of creatinine was not impaired. Similarly the possibility of a significant linear correlation between cGMP levels and blood pressure values or biological data was excluded in these women.Conclusion.Plasma cGMP concentrations are increased in pre‐eclampsia. They decrease to control values when blood pressure returns to normal values; they indicate enhanced guanylyl cyclase activation by ANP and additional factors, but cannot be considered as a direct ind