Body wall protein from the sea cucumber (Acaudina molpadioidea) was hydrolyzed sequentially with bromelain and alcalase. The hydrolysate was fractionated into two ranges of molecular weight (PH-I, >2 kDa; PH-II, <2kDa) using an ultrafiltration membrane bioreactor system. The PH-II brought about a high angiotensin I-converting enzyme (ACE) inhibitory activity. An ACE inhibitory peptide was isolated from the PH-II, using the chromatographic methods including gel filtration, ion-exchange chromatography and reversed phase high-performance liquid chromatography. The purified ACE inhibitory peptide was a novel peptide, showing very low similarity to other ACE inhibitory peptide sequences, and was sequenced as MEGAQEAQGD. It was found that the inhibitory activity of the peptide was intensified by 3.5 times from IC(50) 15.9 to IC(50) 4.5 microM after incubation with gastrointestinal proteases. The ACE inhibitory peptide from A. molpadioidea showed a clear antihypertensive effect in spontaneously hypertensive rats (SHR), at a dosage of 3 microM/kg.