Background: The neurobiology of posttraumatic stress disorder (PTSD) involves alterations in multiple neuroendocrine and neurotransmitter systems. Platelet monoamine oxidase (MAO-B) has been associated with susceptibility to various psychiatric disorders, personality traits, and behaviors. Methods: Platelet MAO-B activity and MAO-B intron 13 polymorphism (a G/A substitution) were determined in male war veterans (n = 106) with DSM-fV diagnosed current and chronic PTSD, divided into subgroups of PTSD patients with (n = 28) or Without (n=78) psychotic features, combat exposed veterans (n=41) who did not develop PTSD, and healthy control men (n = 242). Results: Two-way ANOVAs revealed a significant. effect of diagnosis and smoking, a significant effect of smoking, no significant effect of genotype, and no significant interaction between genotype, smoking or diagnosis, on platelet MAO-B activity. One-way ANOVAs showed significantly lower platelet MAO-B activity in smokers than in nonsmokers. After controlling for smoking, veterans with psychotic PTSD had significantly higher platelet MAO-B activity than veterans with or without PTSD, or healthy subjects. Limitations: The results were obtained on peripheral biochemical marker, i.e. platelet MAO activity. Conclusions: The MAO-B intron 13 polymorphism was not functional, and did not affect platelet MAO-B activity. The allele frequencies of the MAO-B genotype were similarly distributed among healthy controls and veterans with or without PTSD and/or psychotic symptoms. The results suggest that platelet MAO-B activity, controlled for smoking status, might be used as a peripheral marker of the psychotic symptoms in PTSD. (C) 2007 Elsevier B.V. All rights reserved.