Using the aortocaval shunt as a model of chronic volume overload in the rat, changes of the ANF system were analyzed. A constant shunt volume of 57% increased the heart weight after 14 days by 28% (from 917 +/- 16 to 1177 +/- 28 mg, p < 0.001). The ANF plasma concentration increased from 30.4 +/- 15.1 to 108.2 +/- 30.6 pg/ml (p < 0.05), which corresponds to levels which are reached in early stages of heart failure. ANF tissue concentrations, however, were decreased in both atria while no significant change could be observed in the ventricles. The analysis of the ANF-mRNA expression as an indicator for the ANF-synthesis showed significant increase in the ANF-mRNA/Actin-mRNA ratio in the right atrium by 56% and in the left atrium by 63%. In ventricular tissue the relative ANF-mRNA increased by 58% (right) and 83% (left ventricle). Increased ANF plasma levels during chronic volume overload are due to increased atrial and ventricular ANF-synthesis. The induced ventricular mRNA indicates the participation of the ventricles in the humoral response to volume overload.