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Background: Matrix MetalloProteinases (MMPs), particularly #’s 2 and 9, have been implicated in the cascade of proteolytic events that lead to aneurysmal dilation of the aorta; and a recent clinical trial of doxycycline has addressed the potential of an MMP inhibitor to retard the expansion of small AAA’s. However, the rate of AAA expansion was 0.63%/month; and several side effects were noted, including photosensitivity. Accordingly, we have commenced screening other compounds for inhibitory activity against MMP-2, which is the predominant gelatinase produced by cultured AAA fibroblasts. We have concentrated on nutriceuticals that are currently in the human food chain and have GRAS (Generally Regarded As Safe) status in the USA. We tested two products, AneuMastat™, a green tea polyphenol known to inhibit MMPs #2 and #9, and InflaMastat®, a sea cucumber-derived sulfated polysaccharide commercially available in the USA. Methods: Fibroblasts cultured from AAA specimens were lysed, and the protein content of the supernatant was quantified. Substrate gel enzymography (SGE) was used to test inhibitory properties of candidate compounds against MMP-2 of AAA fibroblast origin. Results: InflaMastat® partially inhibited MMP-2 activity (∼80 %) at 100 ug/ml against 30 mg lysate; and when combined with the catechin-containing product AneuMastat™ inhibition was 100% complete under the experimental conditions (no detectable lysis). Further experiments with four additional purified compounds from similar sources suggested that the patterns of inhibition are variable and complex. One agent was 90% effective as an inhibitor at all concentrations studied; while another was inhibitory at low concentrations but exhibited intrinsic gelatinolytic activity at higher concentrations. Conclusion: Although the results of the initial clinical trial of doxycycline as an inhibitor of AAA expansion in man were disappointing, the present experiments suggest that there is a strong rationale for investigation of additional inhibitors of matrix metalloproteinases, which may have greater efficacy and fewer side effects than the recently-trialed doxycycline. [Copyright &y& Elsevier]