Atrial natriuretic factor (ANF) secretion was studied using isolated perfused right atria prepared from rats. Adrenomedullin (ADM), a recently identified 52-amino acid peptide whose biological activity has a striking resemblance to that of ANF, was added to the perfusate at a concentration of 1 microg/ml. The concentration of ANF secreted into the perfusate was measured by radioimmunoassay, under basal conditions (atrial wall unstressed), and during atrial distention (intraluminal pressure raised to 4 and to 6 cm water). It was found that basal secretion of ANF was not altered by ADM. However, when intraluminal pressure was raised, there was a significantly smaller increase in ANF secretion in the ADM-infused atria than in the control atria. It is concluded that ADM significantly reduces stretch-induced secretion of ANF, while having only minimal effects on basal secretion. Such an inhibitory mechanism would ensure the necessary negative feedback mechanism to counter the previously-reported stimulatory actions of ANF on ADM secretion. Moreover, these results support the hypothesis that ADM could be responsible for the reduction in stretch-induced ANF release observed during pregnancy.