Programmed cell death in intersegmental muscles and labial glands of Manduca sexta is a type II form of active cell death, in which lysosomal destruction of cytoplasm is a prominent and early feature, and the collapse of the nucleus is late and relatively modest until the bulk of the cytoplasm has been eroded. The prominent features of this collapse include an early expansion of the lysosomal compartment and a decrease in overall protein synthesis, while a small number of mRNAs persist or are upregulated. Energy resources appear to be adequate during the early stages of degeneration, and changes in levels of second messages likewise do not seem to be sufficiently dramatic to explain the failure of the tissue. There is some suggestion that DNA may not be completely intact long before the labial gland finally collapses, suggesting that it may fail under heavy load. Otherwise, we do not yet have an explanation for the precipitous drop in overall protein synthesis.