Sponges of the genus Xestospongia have yielded a variety of bioactive metabolites. We wish to report the isolation of a new metabolite renierol [4] and the known metabolite mimosamycin [5] from the hard blue sponge Xestospongia cayredoi collected at Sand Island, Suva Harbor, Fiji. Crude methanolic extracts of X. cayredoi showed significant in vitro cytotoxicity against the L1210 murine leukemia line (LC₅₀ 0.05 μg/ml), insecticidal activity against the tobacco budworm (Heliothis virescens), and antimicrobial activity against Staphylococcus aureus (SA-27661), Bacillus subtilis (BS-6051), Escherichia coli (EC-14948), and Saccharomyces cerevisiae (SC-9763). The methanolic extract from the lyophilized sponge (161 g dry wt.) was partitioned via a Kupchan scheme to give hexane, CCl₄, CHCl₃, and MeOH soluble materials. Antimicrobial activity was concentrated in the CHCl₃ fraction, which was subjected to column chromatography (Sephadex LH-20, MeOH-CHCl₃ 1:1) followed by HPLC (Whatman Partisil 10, EtOAc-TMP 1:1) to yield pure renierol [4] (11.3 mg, 7×10⁻³%) as a reddish-brown powder and mimosamycin [5] (15 mg, 9.3×10⁻³%) as a yellow powder. Renierol showed antibiotic activity against S. aureus (100 μg on 6-mm disk gave a 10-mm inhibition ring) and mild cytotoxicity against L1210 (IC₅₀ 3.0 μg/ml). Its molecular formula C₁₂H₁₁NO₄ was confirmed by HRMS, and spectral data (IR, UV, ¹H/¹³C-NMR) were consistent with an isoquinoline quinone structure similar to renierone [6] and 1,6-dimethyl-7-methoxy-5,8-dihydroisoquinoline-5,8-dione [7]. Mimosamycin, assigned the same molecular formula C₁₂H₁₁NO₄, showed antimicrobial activity against S. aureus (100 μg on 6-mm disk gave a 13-mm inhibition ring), with spectral data matching published values (originally isolated from Streptomyces lavendulae and later from Reniera sponges). The low yields of renierol and mimosamycin, their presence in different sponge genera, and mimosamycin's microbial origin suggest these metabolites are derived from sponge bacterial symbionts.