Neural crest mesenchyme participates in the formation of craniofacial structures that are malformed in the fetal alcohol syndrome (FAS). We studied the effects of continuous ethanol treatment (0.05%, 0.10%, 0.15%, 0.20%) on developing neural crest cells in vitro. These cells migrate, but many fail to develop their usual arborized dendrites. Exposure of well differentiated dendritically arborized cells to ethanol only on day 6 for 2 hr and 20 min results in rapid cell retraction and alteration in cell-to-cell contacts. Longer treatment causes loss of substratum adhesion. Monoclonal antibodies against tubulin and actin reveal that these ethanol-induced morphological changes are related to disruption of microtubules and microfilaments. Thus ethanol may exert at least part of its teratogenic effect by interferring with the structure and function of the cytoskeleton.