These experiments examined the effects of altering venous return, aortic pressure, or perfusate sodium concentration on the release of atrial natriuretic factor (ANF) from a rat heart-lung preparation. Changes in perfusate ANF concentration during each time period (delta ANF) were used as an index of ANF secretion. Raising the height of the venous return reservoir from 2-3 to 5-7 cm above the heart increased delta ANF from 88 +/- 19 to 748 +/- 154 pg X ml-1 X 10 min-1 (P less than 0.01, n = 7). In control experiments where the height of the reservoir was not increased, delta ANF was unchanged (65 +/- 35 vs. 43 +/- 26 pg X ml-1 X 10 min-1, n = 6). Increasing aortic pressure from 60 to 100 mmHg increased ANF from 43 +/- 10 to 107 +/- 20 pg X ml-1 X 15 min-1 (P less than 0.05, n = 6). Separate groups of heart-lung preparations were perfused with solutions with sodium concentrations of 132 +/- 1, 144 +/- 2, or 166 +/- 1 meq/l (n = 8/group). delta ANF was 45 +/- 14, 50 +/- 17, and 52 +/- 22 pg X ml-1 X 10 min-1, respectively. These values were not significantly different. These results suggest that ANF plays a role in the control of blood volume and blood pressure but do not support a role for ANF in the control of plasma sodium concentration.