Chemical investigation of the dichloromethane extract of the Red Sea marine sponge Lamellodysidea herbacea led to the isolation of seven new polychlorinated derivatives 3–6 and 8–10 in addition to the known dysidamide 1, dysidamide B 2 and dysidamide C 7. Their structures were established by extensive NMR spectroscopic data. The absolute configuration of compound 9 was determined by X-ray crystallographic diffraction analysis. Dysidamide 1 exhibited neurotoxic effects towards both mesencephalic and cortical murine neurones at 0.8 μg/ml. Seven new polychlorinated derivatives have been isolated in addition to the known dysidamide, dysidamide B and dysidamide C from the Red Sea marine sponge Lamellodysidea herbacea. Their structures were established by extensive spectroscopic methods. Dysidamide exhibited neurotoxic effects towards both mesencephalic and cortical murine neurones at 0.8 μg/ml.