The relationship between the expression of Hox-4 genes in the mesenchyme and the apical ectodermal ridge was investigated in both normal chick wing buds and wing buds treated with retinoic acid. Two conclusions emerge. One is that the activation of Hox-4 domains and the elaboration of Hox-4 gene expression patterns involve cooperation with a signal from the apical ridge. The second is that the domains of expression of 5'-located members of the complex correlate with the maintenance of the thickened ridge which is required for subsequent bud outgrowth.