The incidence of gross chromosomal abnormality was measured in a large (4500), relatively unbiased sample of New Haven infants born during 1 year. The frequency of infants with abnormal chromosomal constitutions was 0.5 percent. For mothers over age 34, 1.5 percent of newborns were chromosomally abnormal. Only one in four of these infants could have been detected by phenotypic criteria alone. Methods are discussed whereby this fraction of the newborn population might be detected and possibly reduced.