Of 452 low-birth-weight infants who were routinely screened for maximum renal acid stimulation (MRAS) (urine pH < 5.4), 149 episodes of incipient late metabolic acidosis (urine pH < 5.4 on 2 consecutive days) were randomly allocated to either a control group or treatment with NaHCO3 or NaCl (2 mmol/kg/day each) for 7 days. Urinary excretion of aldosterone-18-glucuronide (Aldo), arginine vasopressin (AVP) and cortisol was determined in timed urine samples. On day 1, patients with MRAS showed a tendency towards increased urinary excretion of Aldo compared with infants without MRAS. In patients who received alkali therapy, urinary excretion of Aldo, AVP and cortisol decreased or showed a trend to lower values from day 1 to day 7, whereas in patients with MRAS but no specific therapy, Aldo and AVP showed a tendency to increase. We concluded that persistent MRAS is not only characterized by a reduced rate of weight gain and a tendency to decreased nitrogen assimilation, but also increased secretion of Aldo and AVP.