What pattern of brain damage could completely obliterate the sense of olfaction in humans? We had an opportunity to address this intriguing question in Patient B., who has extensive bilateral damage to most of the limbic system, including the medial and lateral temporal lobes, orbital frontal cortex, insular cortex, anterior cingulate cortex, and basal forebrain, caused by herpes simplex encephalitis. The patient demonstrated profound impairments in odor identification and recognition. Moreover, he could not discriminate between olfactory stimuli, and he had severe impairments in odor detection. Reliable stimulus detection was obtained only for solutions of the organic solvent acetone and highly concentrated solutions of ethanol. In contrast to the more circumscribed olfactory deficits demonstrated in patients with damage confined to either the temporal lobes or orbitofrontal cortex (which tend to involve odor identification but not odor detection), Patient B. demonstrated a strikingly severe and complete anosmia. This contrast in olfactory abilities and deficits as a result of different anatomical pathology affords new insights into the neural substrates of olfactory processing in humans.