Objective: The validity of the rule of thumb that infants may have a weight loss of 10% in the first days after birth is unknown. We assessed the validity of this and other rules to detect breast-fed infants with hypernatraemic dehydration. Design: A reference chart for relative weight change was constructed by the LMS method. The reference group was obtained by a retrospective cohort study. Participants: 1544 healthy, exclusively breast-fed infants with 3075 weight measurements born in the Netherlands and 83 cases of breast-fed infants with hypernatraemic dehydration obtained from literature. Results: The rule of thumb had a sensitivity of 90.4%, a specificity of 98.3% and a positive predictive value of 3.7%. Referring infants if their weight change is below -2.5 SDS (0.6th centile) in the reference chart in the first week of life and using the rule of thumb in the second week had a sensitivity of 85.5%, a specificity of 99.4% and a positive predictive value of 9.2%. Conclusions: The rule of thumb is likely to produce too many false positive results, assuming that for screening purposes the specificity needs to be high. A chart for relative weight change can be helpful to detect infants with hypernatraemic dehydration.