The apolipoprotein E allele (Apo-E gene) status was determined in 147 individuals from a longitudinal study. 53 satisfied NINCDS-ADRDA criteria for probable or possible Alzheimer's disease (AD), 37 were non-demented healthy controls. 31 patients with AD had one or two Apo-E 4 alleles (phenotypes 1 x 4-2; 20 x 4-3; 10 x 4-4) compared with only 9 controls (8 x 4-3; 1 x 4-4). Within the AD group, patients homozygous for Apo-E 4 had an earlier onset of illness (7 of 10 cases were presenile) and more severe cognitive impairment at the time of examination after similar durations of illness as patients without Apo-E 4. This may reflect an influence of the Apo-E 4 gene dosage on the onset and course of illness, which is probably independent of chromosome 14 mutations.