Atrial natriuretic peptide (ANP) is synthesized in the kidney but its physiologic significance there is unclear. To determine whether renal expression of the ANP gene is regulated, renal ANP mRNA expression was assessed in remnant kidneys after 5/6 nephrectomy in Munich-Wistar rats. In normal sodium intake groups, ANP mRNA expression in the remnant kidney was significantly increased by 5.0 +/- 0.8-fold (n = 7, mean +/- SEM) at 4 d when compared with sham-operated controls (n = 6, all sham-operated groups) (*P < 0.001 by Scheffe's test) and by 28.3 +/- 5.1-fold at 14 d. This latter response was markedly diminished to 7.6 +/- 2.1-fold (n = 7, versus sham) in rats maintained on a low sodium diet. At 4 d, on the other hand, no significant downregulation was observed with dietary sodium restriction. Because natriuretic peptides have previously been shown by us to play a major role in the adaptive responses of remnant nephrons to renal mass ablation, these data suggest that ANP of renal origin may contribute to the overall mechanism for enhancing sodium excretion in the face of declining nephron number.