The intersegmental muscles (ISMs) of the tobacco hawkmoth Manduca sexta undergo two sequential changes in mass at the end of metamorphosis. Atrophy results in a 40% loss of muscle mass beginning 3 days before adult eclosion (emergence). Coincident with eclosion, the ISMs undergo programmed cell death that results in the complete destruction of the muscles during the subsequent 30 hr. These developmental changes are initiated by sequential decreases in the circulating titer of the ecdysteroids. While the molecular basis of ISM atrophy is largely unknown, the commitment of the muscles to die has been shown to require the repression of specific genes and the activation of others. Data presented here suggest that two of the repressed genes encode the proteins actin and myosin heavy chain. Expression of both actin and myosin heavy chain mRNA was greatly decreased when the ISMs became committed to die. When animals were treated with 20-hydroxyecdysone, cell death was delayed and the loss of these transcripts was reduced. At the protein level, actin expression was reduced by 84% at the time the muscles were committed to die. The reduction in actin and myosin heavy chain synthesis presumably plays a role in the rapid dissolution of the muscles.