The hypothesis of prefrontal dysfunction in psychopathy has been pursued for many years, without convincing results. It is proposed here that this approach in previous studies was far too global. The present investigation was carried out in order to test a more specific hypothesis of orbitofrontal and/or frontal ventromedial deficits in psychopathy. Psychopathic criminals were compared to non-psychopathic criminals with measures related to orbitofrontal or frontal ventromedial functioning, as well as with control measures more associated with frontodorsolateral and posterorolandic functions. All subjects provided urine samples for drug assay. It was found that, while the two groups performed similarly on all the control measures, including the drug tests, the psychopaths were significantly impaired on all the orbitofrontal-ventromedial tasks. The psychopaths were significantly impulsive on several tests as well as significantly dysosmic [corrected]. The latter finding is particularly important in the sense that it cannot readily be explained socioculturally, thus presenting a new and convincing argument for brain-based etiology of this disorder. The results are discussed in relation to other psychiatric disorders characterized by impulse dyscontrol as well as in relation to other putative neurobiological etiological factors in psychopathy.