Mineralocorticoid resistance results from inability of aldosterone to exert its effect on its target tissues. The syndrome is associated with salt loss, hypotension and hyperkalemic acidosis. We have cloned and sequenced the cDNA of the mineralocorticoid receptor of five sporadic cases with this syndrome but have found no mutations of pathophysiological significance, which would explain the resistance of these patients to aldosterone. In all of these patients, we also examined 0.9 kb of the 5' regulatory region and the first untranslated exon of the mineralocorticoid receptor gene, without detecting any abnormalities. We are now studying the subunits of the amiloride-sensitive sodium channel (ENaC), which are in the postreceptor pathway of aldosterone action, in this disease.