Isolated retrograde amnesia is defined as impaired recollection of experiences pre-dating brain injury with relatively preserved anterograde learning and memory. We present findings from a patient (M.L.) with isolated retrograde amnesia following severe traumatic brain injury (TBI) that address hypotheses of the interrelationships of focal neuropathology, episodic memory and the self. M.L. is densely amnesic for experiences predating his injury, but shows normal anterograde memory performance on a variety of standard tests of recall and recognition. The cognitive processes underlying this performance were examined with the remember/know technique, which permits separation of episodic from non-episodic contributions to memory tests by quantifying subjects' reports of re-experiencing aspects of the encoding episode. The results demonstrated that M.L. does not episodically re-experience post-injury events to the same extent as control subjects, although he can use familiarity or other non-episodic processes to distinguish events he has experienced from those he has not experienced. M.L.'s MRI showed damage to the right ventral frontal cortex and underlying white matter, including the uncinate fasciculus, a frontotemporal band of fibres previously hypothesized to mediate retrieval of specific events from one's personal past. Recent functional neuroimaging evidence of an association between right frontal lobe functioning and episodic retrieval demands suggest that M.L.'s memory deficits are related to this focal injury. This hypothesis was supported by right frontal polar hypoactivation in M.L. in response to episodic retrieval demands when he was examined with a cognitive activation H2(15)O PET paradigm that reliably activated this frontal region in both healthy controls and patients with TBI carefully matched to M.L. (but without isolated retrograde amnesia). He also showed increased left inferomedial temporal activation relative to control subjects, suggesting that his spared anterograde memory is mediated through increased reliance on medial temporal lobe structures. Re-experiencing events as part of one's past is based on autonoetic awareness, i.e. awareness of oneself as a continuous entity across time. This form of awareness also supports the formulation of future goals and the implementation of a behavioural guidance system to achieve them. The findings from this study converge to suggest that M.L. has impaired autonoetic awareness attributable to right ventral frontal lobe injury, including right frontal-temporal disconnection. Reorganized brain systems mediate certain preserved cognitive operations in M.L., but without the normal complement of information concerning the self with respect to both past and future events.