The prolific variety of nitrogenous natural products obtained from tunicates (ascidians) portrays these marine animals as specialists in the production of unusual alkaloids. It is noteworthy that some 90% of reported tunicate secondary metabolites are nitrogenous, most having highly modified amino acid or peptide structures. Our interest in the chemistry of tunicates is drawn to these uncommon alkaloids, many with remarkable bioactivity. We report two new cytotoxic alkaloids, varamines A (1) and B (2). Lissoclinum varea (Monniot and Monniot, 1987), a bright red, thinly encrusting tunicate, was collected in shallow waters off the Yasawa island chain, in the Fiji Island group. Assay of the crude methanol extract of this tunicate revealed potent antifungal activity (zone of inhibition of 35 mm in a disk diffusion assay) and cytotoxicity against the L1210 murine leukemia cell line. Solvent partition of the crude extract and extensive chromatographic purification of the chloroform-soluble fraction allowed separation of two brilliant red pigments, varamine A (1) and varamine B (2), both isolated as trifluoroacetate salts. These were readily converted to their respective free bases upon treatment with potassium carbonate. Varamines A (1) and B (2) are tetracyclic heteroaromatic bases, an unusual departure from the secondary metabolites previously reported from Lissoclinum spp. which, typically, are modified thiazole-containing cyclic peptides and macrolides. In fact, 1 and 2 are members of a growing class of marine alkaloids, e.g. amphimedine, obtained from several unrelated marine organisms. Preliminary comparison of the spectral data of 1 and 2 showed the two compounds were related as homologues, and structure elucidation was carried out primarily on the trifluoroacetate salt of 1. Accurate mass measurement of the parent ion at m/z 394.1589 (MH+; Δ = +0.3 mmu) in the fast atom bombardment mass spectrum of varamine A (1) provided the formula C22H27N3O2S. The ultraviolet spectrum of the free base of 1 was richly detailed and revealed strong bands from 232 to 494 nm. In particular, the striking color change from yellow to intense red upon acidification of the free base of 1 was correlated with a reversible bathochromic shift of λmax 464 nm (ε 5170) to 527 (5670).