1. The metamorphosis of the Cecropia silkworm is accompanied by large and systematic changes in the insect's sensitivity to diphtheria toxin.
2. Injection of less than 1 gamma of toxin into mature caterpillars, prepupae, or developing adults causes cessation of development followed by delayed death 1 to 5 weeks later.
3. Dormant pupae, on the contrary, are resistant to 70 gamma of toxin and may survive even this enormous dose for over 4 weeks. One-hundredth of this dose, however, prevents pupae from initiating adult development.
4. Tetanus toxin, to which the insect is insensitive, failed to duplicate any of these effects.
5. Maximal sensitivity to diphtheria toxin is characteristic of those stages in the life history which depend on the presence and function of the cytochrome system. Resistance to the toxin, as in the case of the diapausing pupa, is correlated with the existence and utilization of metabolic pathways other than the usual cytochrome system.
6. This correlation persists within the individual insect. Thus, within the diapausing pupa, the toxin fails to affect the heart in which a normal cytochrome system is absent, but, within the same insect, causes a degeneration of the intersegmental muscles in which an intact cytochrome system is present.
7. These several lines of evidence are interpreted in support of the conclusion that diphtheria toxin acts by blocking the synthesis of one or more components in the cytochrome system.