Summary. The National Children's Study (NCS), which was undertaken in 2000 by collaboration between several US federal government agencies, is one of the largest and boldest longitudinal studies of children's health ever undertaken. One of the key design issues has been the nature of the NCS sample. The paper describes the nature of the choices and the reasons for the decision that the NCS be based on a national probability sample. Designed as a study of the environmental influences on children's health and development, the NCS is expected to identify, enrol and follow about 100000 children from their birth to the age of 21 years. A broad definition of relevant environments of interest, and a full partnership between government, university and medical scientists, introduces considerable challenges in the design of the study.