The genetic interaction between mother and fetus during pregnancy is discussed, focusing on teratogenic alleles that act in the mother to alter fetal development and contribute to a neurodevelopmental disorder. For these alleles, the mother is the genetic patient. Teratogenic alleles interact with modifying and specificity alleles that act in the fetus and with environmental factors. Based on examples of the model, two candidate mechanisms emerge as contributors to neurodevelopmental disorders, folate-homocysteine pathways and immune/inflammatory mechanisms. Both, acting in mothers, affect fetal development and contain many polymorphic genes. These two systems interact with each other. Common functional polymorphisms of mild effect in these two systems of interacting genes are good candidates for teratogenic alleles. The presence of teratogenic alleles complicates gene identification for neurodevelopmental disorders. However, using the special methods required to identify teratogenic alleles is important because this could lead to new approaches to prevention and improved therapy of these disorders. BioEssays 25:464–477, 2003. © 2003 Wiley Periodicals, Inc.