The mechanisms of dementia resulting from small deep infarctions are incompletely understood. The thesis underlying the concept of "multi-infarct dementia" is that multiple lesions have a synergistic effect on mental functions, resulting in dementia irrespective of specific location or volume. In this report, we summarize our experience with six patients reported previously along with additional patients examined subsequently, whose clinical features and brain imaging findings allow an alternative formulation for dementia resulting from lacunar stroke. The six initial patients presented with an abrupt change in behavior after acute infarction involving the inferior genu of the internal capsule documented by computed tomography (CT) and magnetic resonance imaging (MRI). The acute syndrome featured fluctuating alertness, inattention, memory loss, apathy, abulia, and psychomotor retardation suggesting frontal lobe dysfunction. Contralateral hemiparesis and dysarthria were generally mild, except when the infarct extended into the posterior limb. Neuropsychological testing in five patients with left-sided infarcts revealed severe verbal memory loss. Additional cognitive deficits consistent with dementia were evident in four patients. A right-sided infarct caused transient impairment in visuospatial memory. Functional brain imaging in three patients using 133xenon regional cerebral blood flow (rCBF) and single photon emission computed tomography (SPECT) showed focal reduction in hemispheric perfusion most prominent in the ipsilateral inferior and medial frontal cortex. Perfusion was also defective in the medial and laterial temporal cortex. Important pathways of the limbic system traverse the inferior capsule in the region of the genu. Corticothalamic and thalamocortical fibers form the thalamic peduncles which detach from the internal capsule and enter the thalamus at its rostral and caudal poles and along its dorsal surface. The anterior thalamic peduncle, conveys reciprocal connections between the dorsomedial nucleus and the cingulate gyrus, as well as the prefrontal and orbitofrontal cortex. The inferior thalamic peduncle carries fibers which connect the thalamus with orbitofrontal, insular, and temporal cortex, as well as the amygdala via the ansa peduncularis to the ventral amygdalofugal pathway. Thus, damage to one or both white-matter tracts may occur with infarctions in the region of the inferior genu, causing striking frontal behavioral effects and memory loss in our patients associated with functional deactivation of the ipsilateral frontal and temporal cortex.(ABSTRACT TRUNCATED AT 400 WORDS)