Plasma atrial natriuretic factor (ANF) concentrations were measured, and relationships to intracardiac pressures and atrial dimensions were assessed in a series of 17 heart transplant recipients undergoing cardiac catheterization during their annual evaluation. Despite excellent cardiac function (normal filling pressures, adequate cardiac output, ejection fraction above 60%), plasma levels of ANF were elevated. Step-up levels across the heart were consistent with increased cardiac secretion, whereas both the metabolic clearance rate and plasma half-life were normal. Correlations between plasma concentrations of ANF at different cardiac sites and atrial filling pressures were low. However, right and left atrial dimensions in our patients were greatly enlarged. These findings suggest that increased atrial size (by virtue of the atrial anastomoses) and augmented wall stress (law of Laplace) rather than pressure per se are responsible for the increased ANF production after heart transplantation.