Certain clinical aspects of patients with Obsessive-Compulsive Disorder (OCD) appear similar to those of patients with damage to the ventromedial sector of the prefrontal cortex. The hypothesis for the involvement of the frontal region in OCD is also supported by neuropsychological findings. Building on this evidence, we assessed the performance of a group of 34 OCD patients on a measure indexing with orbitofrontal cortex functioning and compared it with the performance of two other subject groups, one consisting of 34 healthy control subjects and the other 16 patients with panic disorder. All study subjects performed a neuropsychological task, which is sensitive to frontal lobe dysfunction and simulating real-life decision-making. Significant differences were found between the neuropsychological profiles of the OCD and of other groups, pointing to a possible specificity of decision-making deficit in OCD. Comparison of the performance of the OCD patients grouped according to response to antiobsessive drug treatment showed that poor neuropsychological task performance predicted poor outcome of pharmacological treatment. Task behavior did not correlate with severity of illness or demographic characteristics of the subjects. Results support the role of the ventromedial prefrontal cortex in OCD.