The measurement of D-dimer in serum samples (s-DD) after standardized coagulation has been reported as a possible single global test for fibrinolysis in unstimulated conditions in healthy subjects and in patients with ischemic heart disease and with different metabolic disorders. No study has been performed on the use of this test in pregnancy, a condition characterized by physiological changes both in coagulation and in fibrinolysis. In this preliminary study, we have evaluated in 28 women with physiological pregnancy and in 23 comparable controls s-DD and a number of markers of coagulation and fibrinolysis. In nonpregnant women s-DD showed a good correlation with fibrinolytic parameters [euglobulin lysis time (ELT) and type 1 inhibitor of tissue plasminogen activator (PAI-1) act: P<.01; tissue plasminogen activator (t-PA) ag and PAI-1 ag: P<.05], confirming previous data, whereas in pregnant women no correlation was observed. Plasma DD (pls-DD) and s-DD levels were not correlated either in pregnant or in control women. s-DD levels were significantly higher than pls-DD in controls and in 15/28 pregnant women whose pls-DD values were in normal range or mildly increased (<110 ng/ml; P<.05), whereas in the 13 pregnant women with high pls-DD levels no significant differences were found between pls-DD and s-DD levels. Because in pregnancy high pls-DD levels are frequently found, possibly only as a consequence of enhanced clotting activation and fibrin deposition, we cannot exclude that D-dimer measured in serum reflects, at least in part, cross-linked fibrin degradation products (FDP) already present in blood before standardized coagulation. Therefore, D-dimer generated in vitro would account only in part for s-DD measured. This can explain why in pregnant women, differently from controls, s-DD does not correlate with fibrinolytic parameters. In conclusion, this preliminary study indicates that baseline pls-DD levels may be an important potential confounder in the interpretation of s-DD results in pregnant women and that s-DD cannot be proposed as a tool for a rapid evaluation of fibrinolytic activity in pregnancy.