In the investigation of potential therapeutics for sulfur mustard (HD), the majority of non-DoD laboratories are limited by regulatory constraints to the use of HD simulants. The University of Michigan Mustard Consortium is uring the half mustard analog 2-chlorethyl ethyl sulfide (CEES) to investigate treatments for HD-induced lung injury. As part of this collaboration, we will evaluate their lead therapeutic for efficacy in rats intratracheally exposed to CEES or HD. Our initial objective was to determine an HD dose that induces lung pathology comparable to a 6 mg/kg dose of CEES. The exposure route and dose of CEES are consistent with that used by the Univesity of Michigan group in the evaluation of therapeutics. Rats were anesthetized with ketamine and rompun, and tracheally intubated. To produce a unilateral left lung injury, a slightly curved PE50 catheter was inserted through the endotracheal tube into the trachea and positioned past the bifurcation into the left mainstem bronchus. Vehicle, CEES (6 mg/kg), or HD (1.4 or 0.7 mg/kg) was administered through the catheter into the left lung at a volume of 100 ul per 250 g rat. Lung histopathology was determined at 24 hr. postexposure. Whole blood samples collected at 6 and 24 hr. were evaluated for cell differentials. Histologic assessment of the exposed lungs showed the injury induced by either dose of HD, or by CEES to be qualitatively indistinguishable. With either toxicant instilled into the lung, brochioles showed sections of epthelium separated from the basement membrane, and inflammatory cells and proteinacious debris occluding the airways. Pulmonary blood vessels showed perivascular edema, and intro-alveolar edema was extensive in exposed areas. Whole blood cell differentials from 6- and 24-hr. post exposure samples showed that at 6 hr. both HD and CEES induced a similar 50-60% decrease in total white blood cell counts. At 24 hr. the counts for the CEES animals had returned to near control levels. In contrast, the HD annimal white cell count was depressed further (75% decrease). This indicates an early difference in response to the CEES and HD despite the similarities in pathology at 24 hr.