The didemnid tunicate Lissoclinum patella collected in Palau produces unique cytotoxic cyclic peptides containing thiazole amino acids, while we now report that L. patella from the Fiji Islands produces a new family of novel thiazole-containing polyketide metabolites, the patellazoles A-C (1-3). The patellazoles were potent cytotoxins in the NCI human cell line protocol with mean IC50 values of 10-3-104 pg/mL and showed antifungal activity against Candida albicans. From 220 g of freeze-dried and pulverized L. patella, a MeOH extract was partitioned, and the active component was concentrated in the CCl4 fraction. Gravity column chromatography on silica gel 62 followed by successive reverse-phase and silica gel HPLC afforded 97 mg of patellazole A (1), 143 mg of patellazole B (2), and 313 mg of patellazole C (3). We report the structure determination of patellazole C (3): its molecular formula C49H77NO13S was assigned by FABMS mass measurement of the MH+ ion (920.5179, required 920.5197). Spectroscopic data (UV, IR, NMR including DEPT, double quantum filtered phase sensitive COSY, 1H-13C chemical shift correlation, INAPT, COLOC, and 2D INADEQUATE experiments) and chemical degradation (ozonolysis to thiazole 4) were used. DEPT experiments established 71 carbon-bound protons (13 methyls, 6 methylenes, 20 methines); D2O exchange experiments indicated six active protons. NMR data indicated an epoxy thiazole moiety, confirmed by ozonolysis. Combination of NMR experiments connected partial structures to establish a 24-membered macrolide. The patellazoles represent a new class of macrolides incorporating an unusual thiazole moiety.