Aim:  We tested the hypothesis that oxytocin in normal man causes natriuresis by means of nitric oxide and/or atrial natriuretic peptide.

Methods:  Normal male subjects were investigated after 4 days of sodium controlled diets (30 mmol sodium chloride day⁻¹, n = 8 or 230 mmol sodium chloride day⁻¹, n = 6). Oxytocin was infused intravenously (1 pmol kg⁻¹ min⁻¹ for 240 min).

Results:  Mean arterial blood pressure, heart rate and glomerular filtration rate by clearance of chromium‐labelled ethylenediaminetetraacetate remained stable. Plasma oxytocin increased from 2 to 3 pg mL⁻¹ to around 50 pg mL⁻¹. Oxytocin decreased urine flow (4.2 ± 0.2–0.75 ± 0.11 and 4.6 ± 1.3–1.4 ± 0.6 mL min⁻¹, low‐ and high‐salt diet, respectively). During low‐salt conditions, oxytocin reduced sodium and potassium excretion (11 ± 2–4 ± 2 and 93 ± 19–42 ± 3 μmol min⁻¹, respectively). Plasma renin, angiotensin II, aldosterone and renal excretion of metabolites of nitric oxide (nitrate and nitrite) all decreased. Plasma atrial natriuretic peptide and cyclic guanosine monophosphate were unchanged. A similar pattern was obtained during high‐salt conditions but in this case the antinatriuresis was not different from that occurring during the corresponding time control series.

Conclusions:  The data reject the hypothesis. In contrast, we found significant antinatriuretic, antikaliuretic and antidiuretic effects, which were not mediated by the renin–angiotensin–aldosterone system, atrial natriuretic peptide, systemic haemodynamics, or processes increasing urinary excretion of metabolites of nitric oxide. The natriuretic effect of oxytocin found in laboratory animals is species‐specific.