To examine the premise that cognitive impairment in Huntington's disease (HD) is related to striatal degeneration, we determined those cognitive deficits most closely associated with linear CT indices of brain atrophy in HD. We systematically evaluated 60 drug-free HD patients who were judged to be in stages I (n = 34) or II (n = 26) of illness. All subjects underwent comprehensive neuropsychological assessment covering a broad spectrum of cognitive operations and standardized head CT imaging for determination of frontal horn (FH), intercaudate (CC), and outer-table (OT) distances. We grouped the cognitive test results, based on a principal-component factor analysis, to form factors 1 (complex psychomotor), 2 (verbal memory), 3 (visuospatial), and 4 (general knowledge). Factors 1 and 3 sharply discriminated between subjects in stages I and II of illness. Factors 1, 2, and 3 correlated strongly with CC/OT, an index of caudate atrophy, whereas only factor 2 correlated with FH/OT, an index of frontal atrophy. These data demonstrate that cognitive impairment is a clear-cut characteristic of early HD that is linked closely to the extent of caudate atrophy as measured by CT.