The aim of this study was to evaluate the short-term and long-term effects of felodipine, a new dihydropiridine calcium antagonist, on arterial blood pressure (BP), the renin-angiotensin-aldosterone system, diuresis, natriuresis, and the atrial natriuretic factor (ANF). In 15 essential hypertensives (WHO class II) BP, venous BP at the posterior tibial vein (VBPTV), diuresis, natriuresis, plasma renin activity (PRA), and both plasma aldosterone and ANF levels were evaluated at the end of a washout period and after two and 24 hours and 30, 90, and 180 days of follow-up with felodipine, 5 mg twice daily. The first dose of felodipine induced a significant decrease in BP, which was associated with increases in both heart rate and VBPTV. An acute diuretic and natriuretic effect, increases in ANF and PRA, and a transient decrease in plasma aldosterone levels were also observed. Throughout the follow-up period, the antihypertensive efficacy remained unchanged, whereas variations in electrolyte balance and hormonal parameters quickly disappeared, except for the increase in PRA, which lasted until the 30th day of therapy. In our study, felodipine showed a great antihypertensive activity during both short-term and long-term treatment. Moreover, the effect of the first dose was characterized by transient increases in circulating ANF and decreases in plasma aldosterone concentrations, which were associated with marked diuresis and natriuresis.