Involucrin is a key component of the cross-linked envelope of terminally differentiated keratinocytes. The human molecule largely consists of 10 residue repeats and forms a thin 460 A long rod. Summarized experimental data and a detailed stereochemical analysis made with computer modeling resulted in a structural model for the involucrin molecule. The suggested structure is a left-handed alpha-helical solenoid built of a tandem array of helix-turn-helix folds. The structure enables us to explain the whole set of experimental data and residue conservations within the repeats. It is ideally suited to serve as a scaffold for cell envelope assembly and proposes a possible mode of the intermolecular interactions of involucrin during cell cornification.