Retinoic acid (RA), a derivative of vitamin A, is essential for normal niammalian development. Developmental abnormalities iriduccd by RA excess and vitamin A deficiencj are different even though thcy affect the same organ systems, and it is clear that there are intraembryonic tissue differences in the requirement for RA. The developmental functions of RA are mediated by its effects on gene expression. In the nucleus, two different forms of RA bind to and activate two families of nuclear receptors, which theinselves co-operate in initiating the transcription of target genes. In this article I propose that the amount of RA reaching the nucleus in different embryonic ti5,sues is modulated by a mechanism involving three cytoplasmic hinding proteins for retinol (CRBP I) and retinoic acid (CRABP I and 11). Abnormalities of craniofacial development resulting from exposure of early ncnral plate stage embryos to KA excess have been studied in some detail; their initial stages involve alteration of both morphological development and the segmentspecific pattern of gene expression in the early hindbrain and its derived neural crest. This system is ideal for studying the relationships between retinoic acid receptors, retinoid binding proteins, and the development of genetic and morphological pattern.