The aim of the study was to evaluate if short-term mineralocorticoid administration activates the circulating kallikrein-kinin systems in normotensive humans and patients with hypertension. Fludrocortisone was given daily for 1 week and circulating components of the plasma and tissue kallikrein-kinin systems and renin-angiotensin-aldosterone system were measured repeatedly. Fludrocortisone increased blood pressure in the normotensive group. A significant reduction in circulating pre-kallikrein and increase in tissue kallikrein occurred only in the normotensive group. Changes in blood pressure in the normotensive group correlated negatively with changes in plasma pre-kallikrein and positively with changes in circulating tissue kallikrein. In the hypertensive group the correlation with pre-kallikrein was non-significant and with tissue kallikrein negative. We conclude that short-term administration of fludrocortisone in moderate doses to normotensive humans induces changes compatible with increased activity in the circulating plasma and tissue kallikrein-kinin systems and that this activation may be abnormal in subjects with primary hypertension.