Digoxin-like inhibitors of Na+,K(+)-ATPase have been implicated in several pathophysiological problems in the perinatal period. Aqueous endogenous digoxin-like immunoreactive substance (DLIS) was extracted from 9 different organs of a 24-week-old human fetus whose mother died after paraquat poisoning. The results indicate that this endogenous DLIS has a wide distribution in fetal tissues. The highest levels were found in gut and adrenals, and there was a correlation between these high levels and the inhibition of Na+,K(+)-ATPase. The hypothesis that DLIS originated in the fetus is of particular relevance.