The manzamines, which have been isolated from marine organisms, comprise a new group of β-carboline alkaloids having intricate polycyclic systems. The provenance of the nitrogen-containing ring systems embraced in the manzamine alkaloids has been problematical since there appears to be no obvious biogenetic path. During our studies on bioactive substances from Okinawan marine organisms, we have isolated two novel alkaloids, ircinals A (1) and B (2), which might be plausible biogenetic precursors of the manzamine alkaloids, from the Okinawan marine sponge Ircinia sp. Here, we describe the isolation and structure elucidation of 1 and 2 as well as two new manzamine congeners, manzamines H (3) and J (4), from the same sponge. Ircinals A (1) and B (2) were converted into manzamines A (5) and J (4), respectively, through Pictet-Spengler cyclization with tryptamine followed by DDQ oxidation. Ircinals A (1) and B (2) and manzamines H (3) and J (4) exhibited cytotoxicity.