The present study was done to investigate the interrelationships between renal kallikrein-kinin, renal prostaglandin E and renin-angiotensin-aldosterone systems in normal subjects and in essential hypertension by means of measuring urinary excretion of kallikrein and prostaglandin E, plasma renin activity and plasma aldosterone concentration before and after stimulation or inhibition of the renin-angiotensin-aldosterone system and inhibition of renal prostaglandin E generation. Urinary kallikrein excretion was increased after the stimulation of the renin-angiotensin-aldosterone system by low Na diet or the administration of furosemide and upright posture, while it decreased after the inhibition of the action of aldosterone by spironolactone. These data show that the change in urinary kallikrein excretion was related to that in the renin-angiotensin-aldosterone system following various stimuli, suggesting that renal kallikrein-kinin system may regulate blood pressure by opposing the action of the renin-angiotensin-aldosterone system. Urinary PGE excretion was decreased after sodium depletion and increased after the administration of furosemide in spite of the augmentation of the renin-angiotensin-aldosterone system. The change in urinary PGE excretion was closely related to that in urinary Na output after various stimuli, and a significant positive correlation was found between basal levels of urinary PGE and those of urinary Na, suggesting that renal prostaglandin E may be involved in the regulation of blood pressure by affecting renal sodium handling. The present data show that basal level of urinary excretion of PGE and kallikrein was lower in essential hypertension than in normal subjects and that the release of renal kallikrein and PGE after the furosemide administration was also suppressed in patients with essential hypertension compared with that in normal subjects, suggesting that there exists, in this disease, an impaired defense mechanism against the renin-angiotensin-aldosterone system resulting in sodium retention.