Background Neuroanatomical data point to functional relationships between the anterior cingulate cortex (ACC) and subcortical centers regulating fear, in particular, the amygdala. Functional brain imaging has disclosed divergent patterns of ACC activation in persons with posttraumatic stress disorder (PTSD). In addition, two preliminary structural imaging studies have found evidence of smaller ACC volume in PTSD. We explored associations between PTSD and ACC volume in a relatively large sample of adult combat veterans in which PTSD, lifetime alcohol abuse/dependence, and Vietnam versus Gulf War service were crossed. Methods Subjects were US military combat veterans of the Vietnam and Gulf Wars recruited from two metropolitan areas served by allied Department of Veterans Affairs PTSD treatment/research centers. Anterior cingulate cortex volume was analyzed as a function of grouping factors with and without adjustment for body size. Results Posttraumatic stress disorder was associated with smaller anterior cingulate cortex volume. This effect persisted in subjects without histories of alcoholism, did not interact with cohort effects, and was not modified by adjustment for body size. Conclusions Anterior cingulate cortex volume is substantially smaller in association with combat-related PTSD, a finding broadly consistent with cingulate hypofunctionality in that disorder