Brevetoxins, the causative agent of neurotoxic shellfish poisoning (NSP) produced by the marine dinofla gellate Karenia brevis, are a significant concern in seafood safety due to the increasing number and severity of red tide events in the coastal southeastern United States. The commercial shellfish industry is particularly vulnerable to these events as a result of the sessile , filter-feeding life cycle of clams and oysters . To prevent NSP, shellfish harvest areas are closed when K. brevis density exceeds 5,000 cells/L and re-opened when the shellfish toxicity assessed by mouse bioassay (MBA) is < 20 MU/100g. Until recently, t he NSP MBA has been the only National Shellfish Sanitation Program (NSSP) approved method for regulatory NSP testing. An ELISA that determines the composite B-type brevetoxins has been approved recently as a limited use method for NSP testing in Eastern oyster (Crassostrea virginica) , sunray venus clams (Macrocallista nimbosa), and hard clams (Mercenaria mercenaria). Brevetoxins are extensively metabolized in hard clams and Eastern oysters. The most persistent and abundant metabolites contributing to overall toxicity are identified as cysteine and taurine conjugates of B-type brevetoxin. These metabolites , BTX-B1, BTX-B2, and S-desoxy BTX-B2, have been identified as biomarkers of brevetoxin exposure in oyster and hard clam and correlate well with the composite toxin measurements by ELISA. In this study, metabolism of brevetoxin in K. brevis bloom-exposed southern hard clams (Mercenaria campechiensis), a species of growing commercial interest, was examined by N2a cytotoxicity assay, ELISA, and LC-MS. Brevetoxins are metabolized in M. campechiensis and the major metabolites are cysteine and taurine conjugates of brevetoxin. R esults suggest that M. campechiensis and M. mercenaria metabolize brevetoxins similarly and BTX-B1, BTX-B2, and S-desoxy BTX-B2 could serve as biomarkers of brevetoxin exposure in M. campechiensis for confirmation by LC-MS.