Two aspects of the chemistry and function of the mesoglea of hydra were studied, (i) Chemical composition: Its component neutral sugars and amino acids were analyzed to determine if this structure contains collagen, (ii) Role in morphogenesis: Hydra were exposed to the lathyrogen 3-aminopropionitrile, an inhibitor of collagen crosslinking, to discover if new cross-linked mesoglea is required for normal regeneration to occur. Large amounts of the neutral sugars glucose and galactose and small amounts of fucose and rhamnose were found, as was the amino sugar glucosamine. Evidence that the major protein component of the mesoglea is collagen was revealed by the detection of hydroxylysine, hydroxyproline, and proline, and of large amounts of glycine. The glucose and galactose are joined as a dimer by an alkali-stable bond to the polypeptide backbone of the collagen. The lathyrogen 3-aminopropionitrile, known to block the assembly of newly synthesized collagen into fibers, causes abnormal head regeneration in hydra. The drug has its maximum effect between 24 and 48 hr after the previous head is removed.