The prothoracic glands of the tobacco hornworm, Manduca sexta, respond to prothoracicotropic hormone (PTTH) by a regulatory pathway involving cAMP, protein phosphorylation, protein synthesis, and enhanced secretion of ecdysteroids including ecdysone and 3-dehydroecdysone. Recent investigations have revealed that PTTH acts by this general mechanism throughout the fifth larval instar, i.e., during the transition from larva to pupa. However, the glands undergo developmental changes in size, steroidogenic capacity, and in elements of the signalling pathway associated with synthesis, degradation, and intracellular action of cAMP. The present review describes such changes, and their possible regulation and consequences, in the general context of endocrine events underlying larval-pupal metamorphosis during the fifth larval stage.