We present the isolation and characterization of seven novel [natural] pyrroloiminoquinones, the makaluvamines A-F (1-6), makaluvone (7), and the known compounds discorhabdin A (8) and damirone B (9) from the Fijian sponge Zyzzya cf. marsailis. The makaluvamines exhibit potent in vitro cytotoxicity toward the human colon tumor cell-line HCT 116, show differential toxicity toward the topoisomerase I1 sensitive CHO cell-line xrs-6, and inhibit topoisomerase I1 in vitro. This activity may be mediated by intercalation into DNA and single-stranded breakage. Makaluvamine A and C exhibited in vivo antitumor activity against the human ovarian carcinoma Ovcar3 implanted in athymic mice. The makaluvamines suggest a plausible interrelationship between the batzelline/isobatzelline and discorhabdin/prianosin classes of compounds.