Erylusamine B (1) has been isolated as an IL-6 antagonist from the marine sponge Erylus placenta Thiele. Its structure was determined by spectral and chemical methods to be N-(5-N, N-dimethylaminopentyl)-14-oxo-22-hydroxy-25-methyl-23-O-β-D-xylopyranosyl-(2→1)-(4-O-acetyl-α-L-arabinopyranosyl)-(3→1)-β-D-xylopyranosyl-(4→1)-2,3,4-O-triacetyl-α-L-arabinopyranosyl)-ε-oxasphingosine. Interleukin 6 (IL-6) is a multifunctional cytokine which exerts a variety of biological functions in various cells through the ligand-receptor interaction. It is also related to such diseases as inflammation, viral infection, autoimmunity, and cancer. Therefore, antagonists for IL-6 receptors are valuable leads. In the course of our search for such leads from Japanese marine invertebrates, we noticed that the MeOH extract of the marine sponge Erylus placenta exhibited antagonistic activity against an IL-6 receptor. Bioassay-guided fractionation yielded an active substance, erylusamine B (1). We describe the isolation and structure elucidation of this metabolite.