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1. The renal effects of amiloride were studied in twenty-six new-born and nine adult dogs, with and without saline expansion. 2. Without saline expansion, amiloride inhibited more sodium reabsorption (normalized to GFR) in puppies than in adults (5.95 vs. 2.18 muequiv/ml. GFR, P less than 0.01). Amiloride inhibited sodium reabsorption more in saline expanded than in nonexpanded puppies (9.39 vs. 5.95 muequiv/ml. GFR, P less than 0.01) but there was no difference between expanded and non-expanded adults. 3. Saline expansion by itself increased fractional sodium excretion (CNa/GFR) more in the adult than in the puppy (0.071 vs. 0.019, P less than 0.01). During amiloride inhibition, saline expansion increased CNa/GFR to 0.045 in the puppy (compared to 0.019 in the nonamiloride inhibited puppy) but saline expansion increased CNa/GFR to the same degree in the amiloride as in the non-amiloride inhibited adult. 4. In all puppies amiloride inhibited more sodium reabsorption than potassium secretion and there was poor correlation between the degree of inhibition of sodium reabsorption and potassium secretion for both the puppy (r = 0.14) and the adult (r = 0.05). 5. Assuming that amiloride acts by inhibiting sodium reabsorption and potassium secretion in the late distal and cortical collecting tubules, these results support the conclusion that in these regions of the nephron of the new-born dog (a) a greater fraction of the filtered sodium is reabsorbed than in the adult and (b) increased fractional sodium reabsorption is responsible, in part, for the attenuated natriuretic response to saline expansion.