Five new alkaloids, lissoclin A (1), lissoclin B (2), lissoclin C (3), lissoclinotoxin C (5), and the dimeric lissoclinotoxin D (6), were isolated along with the known compounds lissoclinotoxin A (4), 2-phenylethylamine (11), and 6-bromotryptamine (12) from Lissoclinum sp. collected from the Great Barrier Reef, Australia. Lissoclin A (1) undergoes photorearrangement to a new benzo-1,3 oxathiazoline 10. The 13C NMR spectrum of 4 is reported for the first time and the structure independently assigned by conversion to the known varacin N-trifluoroacetamide with diazomethane and [13C]diazomethane. Compound 4 is chiral and exhibits unusual stereoisomerism due to restricted inversion about the benzopentathiepin ring. Lissoclinotoxin A (4) and D (6) exhibit antifungal activity against Candida albicans. Since the discovery of amphimedine by Schmitz and co-workers in 1983, pyridoacridine alkaloids have emerged as a class of alkaloids from sponges and ascidians with significant antifungal, cytotoxic, and DNA binding properties. Dercitin, kuanoniamine D, and neoamphimedine were shown to intercalate DNA while neoamphimedine, but not dercitin, inhibits topoisomerase II. Kuanoniamine D and 2-bromoleptoclinidone chelate transition metal ions with high binding constants, a property that may play a role in their cytotoxic effects. Meridine, isolated independently from the ascidian Amphicarpa meridianas and sponge Corticum sp., displays significant antifungal activity against Candida albicans, a property that is related to inhibition of nucleic acid synthesis. The antineoplastic tetracyclic alkaloids varamine A and B and diplaminell are examples of a less common group of sulfur-containing pyridoacridines. β-Carbolines and tetrahydro-β-carbolines, including the eudistomins isolated from several species of tropical ascidians, have shown activity as antitumor and antiviral agents. In this report, we demonstrate secondary metabolism from three distinct biosynthetic pathways within one organism, the blue-white colonial ascidian Lissoclinum sp. from the Great Barrier Reef and the isolation of five new alkaloids; the pyridoacridines, lissoclins A (1) and B (2), the indole alkaloid, lissoclin C (3), and lissoclinotoxins C (5) and D (6). The known polysulfide, lissoclinotoxin A (4), and putative alkaloid precursors, 2-phenylethylamine (11) and 6-bromotryptamine (12), were also found in this organism. Alkaloids 4 and 6 exhibit potent antifungal activity against Candida albicans.