Pericosines A–E 1–5 have been isolated from a strain of Periconia byssoides originally separated from the sea hare Aplysia kurodai. Among them, pericosines C 3 and E 5 were separated as enantiomeric mixtures. Their stereostructures, except for compound 1, have been elucidated or identified on the basis of spectroscopic analyses, including 1D and 2D NMR techniques, and X-ray analysis. In addition, conformation for all the compounds has been discussed. Compounds 1–3 exhibited significant growth inhibition against tumour cell lines. Pericosine A 1 also showed significant in vivo tumour inhibitory activity. In addition, compound 1 inhibited the protein kinaseEGFR and topoisomerase II.