Abstract Intersegmental muscles of the tobacco hornworm, Manduca sexta, degenerate promptly after the ecdysis of the moth. Protein content of the growing, static, and degenerating muscle was evaluated by two-dimensional electrophoresis; RNA was isolated from the muscle and translated, and the translation products likewise analyzed by two-dimensional electrophoresis. Growing and static muscles synthesize predominantly myofibrillar proteins, and small cytosolic proteins constitute a vanishingly small proportion of the proteins identified even by silver staining. When the muscle begins to degenerate, a large number of smaller proteins is seen on the gels. Many of these are apparently fragments of the myofibrillar proteins, but over 30 can be recognized as new translation products. Most of the translation products are found in two regions, one ranging from 20 to 40 kDa and with a p I of 6.5–6.9; and the other approx. 50–70 kDa and p I 5.8–6.2. The pattern is identical in two separate instances of degeneration.