One of the major purposes of newborn screening for 21-hydroxylase deficiency (21OHD) is preventing life-threatening adrenal crisis. However, the details of adrenal crisis in newborns are not precisely documented.e aimed to clarify the clinical details of salt wasting in newborn 21OHD patients. [Methods] Based on the follow-up survey of the screening in Tokyo from 1989 to 2017, we retrospectively analysed the conditions of classical 21OHD neonates before the initiation of therapy.One hundred classical 21OHD patients (55 male, 45 female) were analysed. The age at the first hospital visit was 0-20 days with sex difference (male: 9.0±3.5 days; female: 6.2±3.9 days). Thirty-seven (37.4%) patients exhibited severe salt-wasting (SSW), i.e., Na<130mEq/L, K>7mEq/L or Na/K ratio <20; except for one case, SSW developed in or after the second week of life. The serum concentrations of Na, K, and Na/K were linearly correlated with age in days (R2 = 0.38, 0.25, and 0.34 respectively), suggesting that the risk of SSW increases linearly without a threshold. The age at which the regression lines reached Na<130mEq/L, K>7mEq/L and Na/K<20 was approximately coincided, 11.1, 12.3 and 11.2 days, respectively. All SSW patients exhibited decreased body weight from birth in their second week of life.Our data revealed that the risk of developing SSW increases during the second week of life without a threshold, and for preventing SSW, early intervention, ideally during first week of life, is desirable. An increased body weight in the second week of life indicates the absence of SSW.