The effect of adenosine on atrial natriuretic peptide (ANP) release was studied in the perfused rat heart model. Adenosine had no effect on the heart rate of the spontaneously beating heart at a concentration of 1 microM, whereas at concentrations of 10 and 100 microM it dose-dependently decreased the frequency by 17 and 55% (P < 0.05 and P < 0.001, respectively). In the spontaneously beating hearts, immunoreactive ANP release was inhibited by adenosine at concentrations of 10 and 100 microM (P < 0.05 and P < 0.01). When heart rate was maintained constant by external pacing, inhibition of ANP release was observed only with 100 microM adenosine (P < 0.01). The results show that adenosine dose-dependently inhibits ANP release from the perfused rat heart. The effect of adenosine on ANP release was partially due to its negative chronotropic effect but the results suggest that adenosine may also have a direct inhibitory effect on ANP release in atrial myocardium.