Greater than 120 genes are up-regulated in Xenopus laevis limb buds within the first 24 h after induction of metamorphosis by thyroid hormone. Fourteen of these have been isolated and characterized. Four encode heat shock proteins. The identified regulated genes have in common a relatedness with cell growth as exemplified by the serum response of quiescent fibroblasts. Some of the genes respond directly to hormone. However, the majority appear to be secondary response genes judging from their delayed kinetics and cycloheximide sensitivity. This indicates that there are at least two periods of gene expression change in the first 24 h. DNA replication increases in the second 24 h. Growth of the limb bud occurs for several days before the genes that characterize terminal differentiation of its cell types are up-regulated.