Recognition and treatment of comorbid chronic psychotic symptoms in post-traumatic stress disorder (PTSD) has become of increasing clinical interest. Altered dopamine beta-hydroxylase (DBH) activity has been reported in mood disorders. Plasma DBH is reduced in major depression with psychosis and elevated in bipolar disorder with psychosis compared with their respective non-psychotic diagnostic groups. DBH is likely a trait marker with interindividual variations secondary to genetic polymorphism. We therefore evaluated DBH activity in PTSD patients with and without psychotic features and compared these groups with age- and gender-matched control subjects. Vietnam combat veterans with PTSD (n = 19) (including patients with and without psychotic features) and normal control subjects (n = 22) had plasma DBH enzyme activity assayed photometrically. DBH was significantly higher in patients with PTSD with psychotic features than in patients without psychotic features (80.6 +/- 13.4 vs. 42.1 +/- 7.3 mM/min, P < 0.01) and was also higher than normal control subjects (46.12 +/- 4.93, P < 0.01). Plasma DBH activity may differentiate psychotic and non-psychotic subtypes of PTSD. The observed changes are, interestingly, opposite to those seen in psychotic depression but comparable to psychotic bipolar disorder. Since DBH is a genetic marker, this may reflect individual vulnerabilities to develop psychosis in the context of trauma.