Protein patterns and synthetic profiles were examined during distal regeneration in Hydraoligactis. Electrophoretic and radioactive tracer analyses revealed qualitative changes in the general protein profile during regeneration, with a heightened period of protein synthesis between 27–30 hr of regeneration, immediately preceding emergence of the first pair of tentacles. Following this, an increase in collagen-rich mesogleal protein secretion was observed coincident with tentacle initiation. Inhibition of collagen secretion with the proline analog L-azetidine-2-carboxylic acid (LACA) inhibited tentacle formation, and resulted in the development of unique “hypostome buds” at the distal regeneration surface. At the cellular level LACA did not inhibit the nerve cell differentiation that normally precedes tentacle growth, although some predicted decline in cnidocyte production was noted. It is proposed that mesogleal collagen secretion and structural organization may play a major role in the mechanical aspects of Hydra tentacle morphogenesis.