In the course of my studies of patients with mineralocorticoid hypertensive disorders, unusual presentations led to unexpected findings, both clinically and in steroid etiologies and regulation. Unique circumstances permitted early studies in defining the autonomy of the aldosterone-producing adenoma. A chance referral brought the index case of 17 alpha-hydroxylase deficiency to the research center. New techniques were developed in unusual ways to measure the metabolites of deoxycorticosterone (DOC) using an anesthetic agent. Procedural delays were followed by the surreptitious transfer of a patient from one hospital to the research center after a benign DOC-secreting tumor had been removed. The delay of DOC and all 17-deoxysteroids to respond normally to ACTH stimulation suggested a possible second regulator of DOC. This observation led to studies that demonstrated divergent responses between DOC and cortisol in diverse conditions. An unexplained mineralocorticoid form of hypertension with suppression of renin and aldosterone, but normal DOC production, is seen in licorice intoxication. After licorice was discontinued we documented the delay in the recovery of the inhibited cortisol metabolism (14 days) and renin-angiotensin system (4 months). Licorice extract given to normal subjects on low sodium diets with and without ACTH suppression showed similar results. Other factors in licorice may thus be operative in terms of renin and aldosterone suppression.