The ability to determine chemical warfare (CW) agent exposure is the primary mission for the Analytical Chemistry group at USAMRICD. To best accomplish this, research efforts have focused on developing enhanced screening and definitive analysis methods. Cholinesterase (ChE) screening is the mainstay of the Army’s program for monitoring potential exposures and recovery from organophosphate (OP) compounds. Efforts are underway to increase sensitivity and throughput for various ChE methods. Definitive methods currently in place for OP nerve agents and sulfur mustard (HD) involve gas chromatographic-mass spectrometric assays of hydrolysis breakdown products. For these assays, the window of opportunity for detection is limited to a time frame of several days following exposure. Strategies that enhance the window of opportunity for detection take advantage of interactions of CW agents with relatively long-lived biomolecular targets. The TNO Laboratories developed the procedure of reactivating GB from phosphylated butyrylcholinesterase with fluoride ion. We have applied this procedure to examine plasma and tissues from animals exposed to GB, GD and GF. Experiments from our laboratory with GB and GD indicate that the amount of agent reactivated from plasma samples is greater than the expected or measured quantity of butyrylcholinesterase (BuChE). Since the proposed mechanism of dealkylation (i.e., ageing) for GD would prevent reactivation from BuChE, these data suggest alternative binding sources that may be used to increase the window of opportunity for detection following an exposure. Sulfur mustard forms hydroxyethylthioethyl (HETE) adducts by reacting with carboxylate groups of blood proteins. Based on this observation, a technique for the analysis of the HETE adduct following hydrolytic cleavage from isolated proteins has been developed. The versatility of the technique has been demonstrated since protein from plasma, whole blood or globin from RBCs can be analyzed. In African Green monkeys (Chlorocebus aethiops), the HETE adduct can be detected up to 45 days following an HD exposure of 1 mg/kg intravenously.