Procaine, a local anesthetic, selectively activates the anterior limbic region of the brain, including the anterior cingulate, and may produce powerful emotional and other behavioral responses (including psychotic symptoms) in humans. In a pilot study, we administered intravenous procaine and placebo (saline) to nine combat veterans with PTSD at a dose of procaine known to produce signi®cant behavioral responses in healthy subjects (1 . 38 mg/kg). All but one PTSD patient had mild to moderate, subjective responses to procaine that were statistically elevated on a procaine symptom rating scale ( p 5 0 . 01) compared with saline. Symptoms that occurred only during the procaine infusion included anxiety or euphoria, auditory and visual hallucinations or illusions, and certain physical symptoms such as paresthesias. Two of the nine patients had speci®c PTSD reexperiencing symptoms. However, all patients tolerated the procedure well and, in eight of the patients, symptoms resolved within 5±10 min of procaine administration. One patient had possible dissociative symptoms up to 1 h after procaine that resolved without a recurrence. No patient had a persistent exacerbation of PTSD symptoms. This pilot study suggests that procaine may be a feasible pharmacologic probe to test anterior limbic function in PTSD.