The Fontan procedure results in right atrial distention and is complicated by fluid retention. Since systemic fluid balance may be hormonally mediated in part and related to right atrium size, we measured plasma atrial natriuretic factor and plasma arginine vasopressin levels in 19 patients undergoing the Fontan procedure and in 12 control patients undergoing other types of heart operations. Preoperative plasma atrial natriuretic factor levels were higher in patients undergoing the Fontan procedure than in control patients (95 +/- 16 pg/ml preoperatively versus 50 +/- 8 pg/ml; p less than 0.05) and increased in patients undergoing the Fontan procedure to 330 +/- 48 pg/ml by postoperative day 2 (p less than 0.05) but not in control patients. Increased plasma atrial natriuretic factor levels could enhance capillary transudation, but elevated plasma atrial natriuretic factor levels should also enhance diuresis and prevent fluid retention. Vasopressin levels, however, were also increased in patients undergoing the Fontan procedure (from 9 +/- 2 pg/ml preoperatively to 144 +/- 37 pg/ml at end of operation) and were higher and remained elevated longer than in control patients undergoing heart operations (37 +/- 7, 20 +/- 4, 16 +/- 6 pg/ml on postoperative days 1, 2, and 3 to 10 for the Fontan group compared with 15 +/- 4, 4 +/- 1, 4 +/- 2 pg/ml for control patients). Vasopressin levels were highest in the Fontan group with the most severe fluid retention and effusions (for example, 51 +/- 10 pg/ml versus 23 +/- 4 pg/ml, on postoperative day 1). Increased vasopressin and atrial natriuretic factor could act synergistically to result in the development of effusions after the Fontan procedure when atrial natriuretic factor-induced capillary transudation is combined with vasopressin-induced antidiuresis.