Agnathia-holoprosencephaly (A-H) is a developmental field complex involving a graded series of defects in the jaws, mouth, tongue, ears, eyes, and brain. Two general groups can be recognized: agnathia with holoprosencephaly (more severe) and agnathia without holoprosencephaly (less severe). This report describes three new cases of agnathia without holoprosencephaly and reviews the recent literature. By combining published cases with those ascertained through a survey of genetic centers in the United States, it appears that there have been at least 24 occurrences of A-H in the past 25 years. An inductive defect of the prechordal mesoderm that also affects neural crest cells is presented as the cause for this developmental field complex. Because of the etiologic heterogeneity associated with developmental field defects, the genetic counselor must provide a wide range of recurrence risks when dealing with the A-H complex.