19-Nor progesterone (19-nor P) has previously been shown to have a approximately 3-fold higher affinity for mineralocorticoid receptors than progesterone (P), its C-19 methylated parent steroid; in contrast, 19-nor aldosterone has less than 1% the mineralocorticoid receptor affinity of aldosterone. In the present study we have compared P and 19-nor P, in terms of their mineralocorticoid activity in an adrenalectomized rat urinary K+/Na+ bioassay system. Progesterone, as previously has been shown, is a mineralocorticoid antagonist with no agonist activity. In contrast, 19-nor progesterone is a full mineralocorticoid agonist, with no discernible antagonist activity. Loss of the C19 methyl is thus followed by profound changes in mineralocorticoid activity (aldosterone: agonist to inactive; progesterone: antagonist to agonist). In the light of the recent demonstration of C19 demethylation by the kidney, such changes in mineralocorticoid activity may be implicated in currently unexplained syndromes of sodium retention.