Studies were undertaken in anesthetized male Sprague-Dawley rats to investigate the effects of lowering renal arterial pressure within the autoregulatory range (to 85-95 mmHg) on the renal response to atriopeptin II (AP II) and atrial extract (AE). The natriuresis and diuresis produced by bolus injections of AP II at three dose levels (250-1,000 ng) was abolished or substantially reduced at lowered arterial pressure (85 mmHg). When renal artery pressure was lowered at the same time as an AE infusion was begun it completely blocked the natriuresis and diuresis. When pressure was reduced after 45 min of AE infusion the natriuresis was blunted, but not fully abolished. The effect of prior reduction in renal arterial pressure on the response to AP II (100 ng/min) and furosemide was compared; the AP II natriuresis was prevented when arterial pressure was lowered to 90 mmHg, but the natriuretic effect of furosemide was only slightly diminished. There was no significant rise in glomerular filtration rate (GFR) with AP II and no correlation between GFR changes and the Na excretory response. Reducing renal arterial pressure prior to, at the same time as, or 45 min after beginning an infusion of atrial natriuretic peptide substantially blunts or completely abolishes the natriuresis. Reductions in renal arterial pressure may block the natriuretic and diuretic effects of these compounds by interfering with their hemodynamic actions or by causing sufficient enhancement of salt reabsorption to limit delivery to terminal nephron segments.