The influence of treatment with progesterone and with 4 synthetic progestagens (megestrol-acetate, dydrogesterone, norethisterone-acetate, d-norgestrel) for 6 days on sodium balance and on different factors of the renin-aldosterone system was investigated in 20 young healthy men on a fixed sodium intake (83 mEq/day). 50 mg of progesterone im caused, as expected, natriuresis, an increase in plasma renin activity (PRA), plasma angiotensin II concentration (PAC) and aldosterone excretion (AER), while plasma renin substrate concentration (PRS) remained unchanged. Progesterone levels during treatment were somewhat lower than in the luteal phase of normal menstrual cycles in women. Megestrol-acetate (15 mg/day) did not influence sodium balance, but led to a slight increase in PRA and AER after 3 days of treatment. PAC and PRS remained unchanged. Dydrogesterone (30 mg/day) caused slight sodium retention after 3 days of treatment and a concomitant increase in PRA, PAC (upright posture) and AER, but PRS was not different from control. Norethisterone-acetate (30 mg/day) induced a slight natriuresis, an increase in orthostatic PRA and a marked increase in AER. PAC did not change, but PRS increased significantly indicating estrogenic properties of this compound. d-norgestrel (1.5 mg/day) led to a significant increase in sodium and potassium excretion after 5 days of treatment, while AER was slightly increased, PRA and PAC falling below control levels. PRS did not change. Increased AER (excretion of aldosterone-21-glucuronide) during treatment with norethisteroneacetate or d-norgestrel may indicate altered aldosterone metabolism.