Quantitative analyses were performed on computer tomography (CT) scans from 7 patients with Korsakoff's syndrome, 7 age-matched alcoholic subjects, and 7 age-matched healthy control subjects. CT values were used to estimate tissue density and fluid volume in specified brain areas. Tissue density was assessed by averaging CT values in small (5 x 5 mm) areas sampled bilaterally in 6 specified areas--thalamus, head of the caudate nucleus, putamen, anterior white matter, posterior white matter, and centrum semiovale. We assessed fluid volume using a semiautomated computer algorithm that estimated the proportion of fluid in 7 brain regions--total ventricular space, third ventricle, interventricular region, frontal sulci, peri-Sylvian region, medial cerebellum, and vertex. For the patients with Korsakoff's syndrome, we also assessed the correlation between CT measures and performance on 6 cognitive and 12 memory tests. Compared with alcoholic subjects and healthy control subjects, patients with Korsakoff's syndrome had lower CT density values bilaterally in the region of the thalamus and had greater estimated fluid bilaterally in the region of the third ventricle. Alcoholic and healthy control subjects did not differ on these measures. Significant cortical atrophy in frontal sulcal and peri-Sylvian areas was detected both in patients with Korsakoff's syndrome and in alcoholic subjects. For patients with Korsakoff's syndrome, impairment on behavioral tests, and on memory tests in particular, was correlated with low-density values in the thalamus and with high fluid values in the region of the frontal sulci. Damage to diencephalic and frontal areas may especially contribute to the memory and cognitive impairment exhibited by patients with Korsakoff's syndrome.