Cultured keratinocytes afford an excellent opportunity to study the influence of retinoids on the behavior of a stratified squamous epithelium and the interaction of keratinocytes with substrate. We have found that all-trans-retinoic acid retards the formation of colonies, does not influence attachment, and causes increased shedding of cells from the cultures. Retinoids do not influence the relative abundance of the keratin polypeptides. Our observations are on human neonatal foreskin-derived keratinocytes grown in Dulbecco's modified Eagle medium containing 20% fetal bovine serum. Because fetal bovine serum contains vitamin A, our findings represent differences between low and high levels of vitamin A.