Skeletal muscle atrophy and death are protracted processes that accompany aging and pathological insults in mammals. The intersegmental muscles (ISMs) from the tobacco hawkmoth Manduca sexta are composed of giant fibers that undergo distinct hormonally-regulated programs of atrophy and death at the end of metamorphosis. Atrophy occurs during the three days preceding adult emergence and results in a 40% reduction of mass, while death takes place during the subsequent 30 hours and results in the complete loss of the fibers. There are no significant changes in tetanic force or calcium sensitivity in skinned fiber preparations during atrophy. However, the size of caffeine-induced contractions fell by about 50%. With the onset of the death phase, dramatic reductions occur in ISM: tetanic force, twitch amplitude, resting potential, caffeine-induced contractions, calcium sensitivity, and Hill coefficients. Several lines of evidence suggest that ISM atrophy is caused by an increase in protein turnover without significant modification of fiber organization. In contrast, ISM death is accompanied by disorganization of the contractile apparatus and concomitant loss of contractile function.