Human cord serum contains substantial amounts of materials that cross-react in radioimmunoassays for digoxin. The average content of digoxin-like immunoreactivity in mixed cord serum is 0.3 +/- 0.05 ngE/ml compared to less than 0.05 ngE/ml in serum from normal adults. After solvent extraction, the major digoxin-like materials present in cord serum coelute on Sephadex LH-20 column with the steroid sulfate fraction. The steroid sulfates are digoxin-like materials because they cross-react in the digoxin RIA. If the amount of dehydroepiandrosterone sulfate, 16 alpha-hydroxydehydroepiandrosterone sulfate, and 15 beta-hydroxydehydroepiandrosterone sulfate present in cord serum and the amount of digoxin-like material present in the same serum are considered, then up to 90% of the digoxin-like materials present can be accounted for on the basis of the steroid sulfates present. However, although steroid sulfates contribute to the digoxin immunoreactivity in both serum and breast cyst fluid, digoxin-like materials are present in breast cyst fluid that are not present in cord serum.