A new series of polychlorinated amino acid derivatives were isolated from the tropical marine sponge Dysidea herbacea (Dictyoceratida) collected at Pohnpei and Palau. Two major hexachlorinated metabolites, dysideathiazole (4) and N-methyldysideathiazole (5), and a minor pentachlorinated compound, 10-dechloro-N-methyldysideathiazole (6), were isolated from a Pohnpei specimen. From Palauan specimens, 10-dechlorodysideathiazole (7), 9,10-didechloro-N-methyldysideathiazole (8), and dysideapyrrolidone (9) were obtained as minor or major constituents. The structures of 4-9 were elucidated by spectroscopic methods (COSY, XHCORR, COLOC, spin-spin decoupling). The absolute stereochemistry of compounds 4-6 was determined by X-ray crystallography of the natural products and of the carbamate derivative 17 to be S at all chiral centers. These polychlorinated compounds are associated with the sponge's major prokaryotic symbiont Oscillatoria spongeliae, providing support for the symbiont's role in their biosynthesis. The absolute configuration determination resolved previous ambiguities from studies of dysidenin and isodysidenin, confirming the correct stereochemistry as S at key chiral centers. Dysideapyrrolidone (9) shares structural features with cyanobacterial metabolites, further supporting the symbiont hypothesis. The compounds show fish-feeding deterrent activity, suggesting a role in enhancing the sponge-cyanobacterium symbiosis fitness.