During our search for new manzamine-related alkaloids, we have isolated nakadomarin A (1), a novel furan-containing hexacyclic alkaloid consisting of an unprecedented 8/5/5/5/15/6 ring system, and ma'eganedin A (2), a new tetrahydro-β-carboline alkaloid with a methylene carbon bridge between N-2 and N-27, from an Okinawan marine sponge Amphimedon sp. EtOAc-soluble fraction of the sponge Amphimedon sp. collected off Kerama Islands, Okinawa, was purified by silca gel and alumina column chromatographies to afford nakadomarin A (1, 1.8x10^<-3>%, wet weight) and ma'eganedin A (2, 9x10^<-4>%) together with several known manzamine alkaloids. The structures containing relative stereochemistry were elucidated on the basis of mainly 2D NMR data. Absolute configurations of ma'eganedin A (2) were deduced as 1R, 10R, 11S, 12R, 24S, 25R, and 26R from the CD Cotton curve. Since nakadomarin A (1) and ircinal A possess the common structures, nakadomarin A (1) may be generated from ircinal A through retro-Mannich, Mannich, and dehydroxylation processes. On the other hand, ma'eganedin A (2) may be biogenetically derived from ircinal B.