AIMS: To determine the potential use of a digoxin-immunoreactive substance in the prediction of preeclampsia, to study the relationship between serum levels of this substance and gestational age, and to evaluate the correlation between this substance and blood pressure findings in preeclamptic pregnancies. METHODS: Serum digoxin-immunoreactive substance concentrations were measured by RIA (double antibody, radioimmunoassay) in normotensive (n = 14) and preeclamptic (n = 17) pregnant women in their third trimesters. Statistical evaluation was performed with the Mann-Whitney U-test and correlation-regression analysis. RESULTS: The mean (+/- S.E.) digoxin-immunoreactive substance levels in the normal and preeclamptic patients were 0.29 +/- 0.06 and 0.31 +/- 0.05 ng/ml, respectively, the slightly higher level in the hypertensive group being statistically non-significant. Serum digoxin-immunoreactive substance levels did not demonstrate good correlation with gestational age and systolic blood pressure in preeclamptic pregnancies. CONCLUSIONS: An endogenous digoxin-immunoreactive substance is present in the sera of third trimester pregnant women, but it does not contribute to the pathogenesis or prediction of preeclampsia.