To study the effect of cardiac tamponade on plasma concentrations of atrial natriuretic peptide (ANP) female calves received an infusion of 450 ml of 0.9% saline into the pericardial space. This was accompanied by a parallel rise in both, right atrial pressure (from 4.5 +/- 2.6 mm Hg to 14.1 +/- 3.8 mm Hg (p less than 0.01] and in intrapericardial pressure (from 0.4 +/- 2.0 mm Hg to 12.9 +/- 3.9 mm Hg (p less than 0.01] and a fall in cardiac output from 11.4 +/- 1.9 l/min to 8.5 +/- 2.4 l/min (p less than 0.01). Plasma concentrations of ANP remained unchanged in 7 of 9 experiments. During these seven experiments plasma concentrations of renin and aldosterone increased from 0.65 +/- 0.27 X 10 E-4 GU/ml to 1.04 +/- 0.43 X 10 E-4 GU/ml (p less than 0.01) and from 2.7 +/- 0.9 ng/dl to 11.4 +/- 6.1 ng/dl (p less than 0.01), respectively. On two occasions, which were characterized by an excessive fall in cardiac output (to less than 40% of initial values) cardiac tamponade was followed by an extensive rise in the plasma concentrations of ANP, renin and aldosterone. These results indicate that an increase in intra-atrial pressure per se is not the decisive factor in the control of ANP secretion. Since atrial transmural pressure does not change during cardiac tamponade ANP concentrations are, as a rule, unaltered by that condition. An increase in plasma ANP is seen only during preshock hemodynamic conditions possibly due to a reduced intra-atrial volume.