Xestamines A [1], B [2], and C [3], which are pyridine alkaloids substituted by C₂₅, C₂₁, and C₂₂ aliphatic methoxylamines, respectively, have been isolated from the marine sponge Xestospongia wiedenmayeri. The structures of these compounds are elucidated by a combination of spectral methods and chemical modification. Marine sponges of the genus Xestospongia (Phylum Porifera, Class Demospongiae, Order Haplosclerida, Family Petrosiidae) have been known to contain a variety of unique alkaloids (1–4), terpenoids (5–7), terpenoid glycosides (8), pentacyclic quinones and hydroquinones (9–13), and straight-chain metabolites (14–19). We now report the isolation of three new alkaloids, xestamines A [1], B [2], and C [3], from our collection of Xestospongia wiedenmayeri, Van Soest (20). The xestamines, which all possess a long aliphatic chain terminated by a β-substituted pyridine and an unusual N-methyl-N-methoxylamine, are structurally related to the cytotoxic niphatynes A [4] and B from Niphates sp. (21); however, they were found inactive against P-388 cells in vitro.