Lissoclinum spp. ascidians have become well-known as prolific producers of cytotoxic cyclic peptides with highly modified amino acid residues (e.g., ascidiacyclamide, ulithiacyclamide) and macrolides with mixed polyketide/peptide biosynthesis (e.g., patellazoles, bistramide A). As part of our continuing effort to isolate biologically active compounds from this genus of ascidians, we collected a sample of Lissoclinum bistratum in the Philippines. The organism lacked any of the metabolites previously described from this organism, but contained a novel family of cyclic hexapeptides (1, 2) containing oxazole (Ozl) residues—a modified amino acid not previously seen in the vast array of modified cyclic peptides previously reported from this genus. Oxazoles from marine invertebrates were first reported from nudibranch egg masses (ulapualides, halichondramides, kabiramides) and subsequently from several sponges (hennoxazoles, bengazoles, calyculin A, orbiculamide A, keramamide). This finding expands our understanding of the biosynthetic capabilities of L. bistratum ascidians (and their symbiotic unicellular alga, Prochloron). Cyclic hexapeptides, bistratamides A and B (3, 4), have been reported previously from L. bistratum collected off the Great Barrier Reef, Australia. These peptides possess the modified amino acid residues methyloxaline (mom), thiazole (Tzl), and thiazoline (Tzn). In addition, a quite similar hexapeptide 5 was recently reported under two different names from both L. bistratum (cycloxazoline) and the terrestrial cyanobacteria, Westiellopsis prolifica (westiellamide), providing circumstantial evidence that the peptides found in the ascidians may be, at least in part, synthesized by the harbored Prochloron. We report here the structures of the oxazole-containing hexapeptides, bistratamides C and D (1, 2). Bistratamide D showed depressant effects when introduced directly into the central nervous system of mice by intracerebral injection; at a 65 pg dose, mice exhibited decreased motor activity, sluggishness, and sedation relative to control.