To determine whether reduced renal mass in the newborn results in acceleration of normal renal development, the response to unilateral nephrectomy (N) before 36 h of age was compared with sham-operated (S) guinea pigs during the period of most rapid nephron maturation. Studies were performed at 7-13 days (group I) and 19-25 days (group II). Mean arterial blood pressure (AP), left kidney glomerular filtration rate (LKGFR), and urine sodium excretion (UNaV) were measured. Superficial single nephron GFR (sSNGFR) and proximal fractional water reabsorption (FRH2O) were measured by micropuncture, and the number of glomeruli (NG) was determined by India ink perfusion. In view of the susceptibility of the neonate to extracellular fluid loss, groups I and II were plasma infused to maintain euvolemia and group II was compared with 19- to 25-day-old hydropenic animals (group III). Increase in body weight with age was unaffected by neonatal N. In group IN, the compensatory increase in sSNGFR was greater than SNGFR for deeper nephrons, which normally contribute most to GFR at this age. In group IIN there was an 80% adaptive increase in LKGFR that could not be entirely explained by the rise in SNGFR. Since NG in group IIN was greater than in group IIS and similar to that in adulthood, the enhanced adaptation in LKGFR in group IIN may be due in part to earlier recruitment of a population of underperfused glomeruli. FRH2O did not change significantly with age and did not differ in N and S groups. Animals in group III developed a rise in hematocrit during the experiment, and AP, LKGFR, and UNaV were lower in group IIIN than in group IIN. Apparently, following N at birth, the sequence of renal functional maturation is accelerated while glomerulotubular balance is preserved. As a result of these adaptive changes, homeostasis is maintained and body growth proceeds without impairment.