Low-dose heparin has achieved wide use for the prevention of deep vein thrombosis. Full-dose heparin (20,000 U/day or more) has a well-documented suppressive effect on adrenal aldosterone production. To determine whether this effect may also occur with low-dose heparin, 5 healthy male volunteers were given heparin, 5,000 U subcutaneously every 12 h for 10 days, and their renin-aldosterone axis was studied. Plasma aldosterone fell from a mean of 17.2 ng/dl at baseline to 6.6 on day 5 and 4.3 on day 10. The 24-hour urinary aldosterone fell from 11.5 micrograms/day at baseline to 5.3 and 6.8 on days 4-5 and 9-10, respectively. After stimulation with furosemide (60 mg orally) and 4 h ambulation, plasma aldosterone remained suppressed on heparin: 22.4 ng/sl at baseline, 7.0 on day 5 and 6.2 ng/dl on day 10. Plasma renin activity, serum and urinary electrolytes, and body weight were unchanged during the study. Hence, low-dose heparin can inhibit aldosterone production. Patients receiving this treatment should be observed (during and after therapy) for impaired electrolyte homeostasis.