Pieces of dorsal neural tube (stages 22-23) or late neural crest tissue (stages 24-26) of Xenopus laevis were cultured. Migratory cells moved out of explants to form an outgrowth of multipolar melanophores on the substratum. Treatment with beta-galactosidase (0.1-0.4 U/ml) to remove cell surface galactose was correlated with detachment of melanophores. In the presence of lower concentrations of this enzyme the shapes of these cells were converted to arborized, spidery morphologies and cell movement was inhibited. Unpigmented cells were affected more slowly. Neuraminidase treatment, to remove cell surface sialic acid and expose more galactose, only affected melanophores. These became increasingly spread on the substratum and cell overlap was observed. These results suggest that the relative amounts of galactose and sialic acid at the cell surface become increasingly important in controlling cell adhesion as X. laevis neural crest cells migrate and differentiate into melanophores.