The role played by the relative degree of expansion of the intravascular and extravascular compartments in limiting the natriuretic response of fluid-loaded developing animals was determined in 1-, 2-, 3- and 6-wk-old puppies. Volume expansion was induced by infusing either isotonic saline, 10% body weight or isoncotic albumin in saline 5% body weight, and measurements of glomerular filtration rate, sodium excretion, fractional excretion of sodium, and plasma volume were made. Each expansion procedure resulted in an increase in the absolute excretion of sodium at all ages (P less than 0.001). The greatest natriuretic effect was observed in the 3-wk-old puppies, the average of the two solutions being 19, 30, 70, and 28 muEq/min/kg in the 1, 2, 3, and 6-wk-old animals, respectively. The difference in natriuresis among the age groups was due predominantly to differences in the magnitude of the increase in fractional excretion of sodium. At all ages, a greater absolute excretion of sodium was encountered during volume expansion with saline than observed with albumin (P less than 0.05). The intravascular volume increased by a similar % at all ages (P greater than 0.1), and saline and albumin yielded equivalent degrees of intravascular expansion (approximately 50%). The results demonstrate that age-related changes in natriuretic response to volume expansion cannot be attributed to differences in either the degree of expansion or the distribution of the load. In addition, the observations indicate that the mechanism underlying the difference between the response to isotonic saline and isoncotic albumin in saline is already operative at birth, and that it is independent of nephron heterogeneity since the proportion of superficial nephrons must have changed during the period of nephrogenesis. The collecting duct, which is sensitive to both isotonic saline and isoncotic albumin, is likely to be responsible for the parallel development of the renal response to these two methods of intravascular volume expansion.