β-Carbolines, biogenetically readily derivable from tryptophan, are a familiar structural feature of marine alkaloids, whereas α-carbolines (also derivable from tryptophan) are rare, with grossularines from a tunicate as the only previous example. We report the structure of kapakahine B, a cyclic hexapeptide isolated from the marine sponge Cribrochalina olemda collected at Pohnpei, Federated States of Micronesia. It contains a tryptophan-derived α-carboline as part of a fused tetracyclic system including a phenylalanine-derived (Phe-2) imidazolone. Another tryptophan (Trp-1) links via its indole nitrogen to a ring juncture of the α-carboline and forms a peptide bond with Phe-1 (bearing a free amino group). The molecular formula C₄₉H₅₄N₈O₆ was determined by HR-FABMS. Its structure was elucidated using ¹H/¹³C NMR (HMBC, COSY, ROESY), amino acid analysis, and Edman degradation, revealing the amino acid sequence and a 16-membered ring formed by a C-N bond between Trp-1's indole nitrogen and C-34. Kapakahine B showed moderate bioactivity against P388 murine leukemia cells with an IC₅₀ of 5.0 μg/mL. The absolute stereochemistry of Ala and Leu was determined as L by Marfey's method.