The apolipoprotein E (APOE) epsilon 4 allele has been consistently found to be frequent in patients with progressive degenerative dementia of the Alzheimer type (DAT). Vascular dementia (VD) may occur as strokes superimposed on presymptomatic DAT, in which case APOE-epsilon 4 frequency should also be increased in VD. We have examined the distribution of APOE-epsilon 4 in patients with DAT (n = 176) or VD (n = 74) and controls (n = 133), and evaluated the risk of dementia associated with APOE-epsilon 4. APOE-epsilon 4 allele frequency was 27% in DAT patients, 21% in VD patients, and 11% in controls. The difference in the distribution of the epsilon 4 allele between DAT or VD patients and controls was statistically significant (chi(2) test, p < 0.05), with a 3.6- and 2.1-fold risk of dementia in DAT and VD patients carrying an epsilon 4 allele. The result that the APOE-epsilon 4 allele is more frequent in DAT patients than in controls, with VD patients falling in between, is consistent with the assumption that VD is a heterogeneous condition, with some patients having an underlying preclinical brain degeneration, in whom the dementia was precipitated by strokes.