Urinary kallikrein excretion was measured by a radiochemical esterolytic assay in patients with essential hypertension or primary aldosteronism. Patients with essential hypertension excreted significantly less (P < 0.001) kallikrein than did normal subjects when they were allowed an ad libitum sodium intake or given 259 mEq sodium/day. When sodium intake was changed from ad libitum to 9 mEq/day, kallikrein excretion increased in the majority of patients with essential hypertension, but it remained significantly less (P < 0.001) than that in normal subjects; however, aldosterone excretion was similar in both groups. Fludrocortisone, 0.5 mg/day for 10 days, increased kallikrein excretion in three patients with essential hypertension. In patients with primary aldosteronism, mean kallikrein excretion was sevenfold higher (P < 0.001) than that in patients with essential hypertension; kallikrein excretion remained unchanged when dietary sodium was altered, but it was decreased by treatment with spironolactone. Mean kallikrein excretion in patients with primary aldosteronism was also significantly higher (P < 0.001) than that in a normotensive control population. The results show that kallikrein excretion reflects the effective level of circulating sodium-retaining steroid in patients with primary aldosteronism but suggest that it is relatively unresponsive to endogenous sodium-retaining steroid in patients with essential hypertension. The data raise the possibility that the kallikrein-kinin system is of pathogenetic significance in human hypertensive disease.