<jats:title>Abstract</jats:title><jats:p>The defensive secretion of the nudibranch <jats:italic>Phyllidia varicosa</jats:italic> consists of two isocyanosesquiterpenes: the previously described 9‐isocyanopupukeanane (<jats:bold>1</jats:bold>), and its 2‐isomer (<jats:bold>4</jats:bold>), for which we report the structure and properties. The mixture originates with a sponge, <jats:italic>Hymeniacidon</jats:italic> sp., where it is produced in varying proportions. CD. measurements and X‐ray diffraction data establish the absolute configuration of the two metabolites.