Should a warfighter potentially be exposed to a chemical warfare agent (CWA), a critical requirement exists for the verification of that event using highly sensitive and selective analytical techniques such as mass spectrometry. Only recently have a small number of laboratories worldwide pursued the development of CWA verification methods in biomedical samples such as urine and blood. Since most CWAs are rapidly hydrolyzed in aqueous solution, our initial method development focused on breakdown products. These compounds are relatively nonvolatile and require derivatization prior to analysis using gas chromatography (GC). Using deuterated forms of the compounds as internal standards and electron impact mass spectrometry (MS) for detection, we were able to quantitatively measure the hydrolysis products of several nerve agents and vesicants at the low ng/ml concentration range. The compounds were rapidly excreted in the urine of several animal models over a period of a few days. More recently, we have pursued the development of MS techniques for the identification of products resulting from the interaction of CWAs with endogenous biomolecules. Adducts of biomolecules are generally stable and provide an opportunity to verify a CWA exposure much longer after the actual event has occurred. A quantitative method is being developed in which the adduct generated from the reaction of sulfur mustard (HD) with plasma proteins is released, derivatized, and then analyzed using GC/MS. The quantity of adducts formed from the reaction of HD with free carboxylic acid sites of plasma proteins should be more abundant than the reaction of HD with terminal valine or cysteines. The addition of base to protein with the HD adduct resulted in the release of thiodiglycol. The thiodiglycol was derivatized with pentafluorobenzoyl chloride and analyzed using GC with negative ion chemical ionization MS to produce a very sensitive, quantitative method. Detectable levels in blood were still observed 45 days after exposure in a nonhuman primate receiving a 1 mg/kg, IV dose of sulfur mustard. We are also analyzing phosphylated plasma proteins resulting from nerve agent exposure using the fluoride reactivation method developed by the TNO laboratory in the Netherlands. The method regenerates the parent nerve agent, which is then easily analyzed using GC/MS. It is being evaluated as a quantitative method for low dose exposure to nerve agents. In a guinea pig model, animals were exposed to the nerve agents sarin and soman. Both plasma and tissue samples generated abundant levels of reactivated nerve agent following a series of low dose, subcutaneous exposures. Reactivation levels were found to decrease rapidly after time of exposure, although they were still measurable after three days. In postmortem samples, the rate of decrease was slower. Taken together or in part, the analytical methods presented here provide a mechanism for verifying a chemical warfare agent exposure using biomedical samples such as blood or urine.