OBJECTIVE Recent studies suggest that urodilatin from the kidneys rather than atrial natriuretic factor from the heart is the more important member of the family of natriuretic peptides involved in the normal regulation of renal sodium and water excretion. We thus examined the relationship between natriuresis, urodilatin, and atrial natriuretic factor in patients after cardiopulmonary bypass, a procedure known to increase levels of atrial natriuretic factor significantly. METHODS Excretion rates of sodium and water were correlated with the excretion of urodilatin and with circulating levels of atrial natriuretic factor, antidiuretic hormone, aldosterone, and plasma renin activity during a period of 16 hours in 12 patients having had coronary artery bypass operations and with approximately a 400% elevation in levels of atrial natriuretic factor. RESULTS Natriuresis did not correlate with atrial natriuretic factor, antidiuretic hormone, aldosterone, or plasma renin activity. Excretion rates of urodilatin, however, correlated significantly with excretion rates of sodium (r = 0.74, p = 0.03), urine flow (r = 0.83, p = 0.01), and with levels of serum sodium (r = 0.82, p = 0.01). CONCLUSIONS These results suggest an important role for urodilatin, greater than that of atrial natriuretic factor, in the regulation of renal excretion of sodium and water after cardiopulmonary bypass surgery.