To determine the susceptibility of aged individuals to chemical warfare nerve agents (CWNAs), we evaluated the 24-hour median lethal dose (LD50) of soman (GD) in adult (2 months of age) and aged (18 months of age) male F344 rats, Aged rats proved more sensitive to GD-induced lethality with an LD50 of 50.0 mug/kg (95% CI; 63.8-78.00). To determine the etiology of theses differences, we measured whole blood and brain acetylcholinesterase (AChE) as well as plasma carboxylesterase (CaE) activity in nave aged and adult rats. Whole blood AChE revealed no differences; however, an 18% decrease in baseline plasma CaE activity was observed in aged rats compared to adult rats. Brain AChE was modestly reduced in aged compared to adult rats in the frontal cortex (82%0, hippocampus (89%), striatum (92%), thalamus (91%), and pons (83%). Furthermore, aged rats showed a significantly greater sensitivity to the toxic effects of GD, displaying seizures and higher mortality rates at lower doses compared to adult rats. This increased sensitivity of aged rats to the toxic and lethal effects of GD has implications for dosing and efficacy of medical countermeasures in aged populations.