Apolipoprotein E type epsilon 4 alleles are increased in both Alzheimer's disease (AD) and cortical Lewy body dementia, while the epsilon 2 allele has been associated as a protective factor against the development of dementia in AD. We have determined APOE genotype in schizophrenic patients coming to autopsy (age range 19-95 years). The allele frequencies in this group were: epsilon 2, 6.0%; epsilon 3, 67.9%; and epsilon 4, 26.2%. Three patients (14%) were homozygous for the epsilon 4 allele. Thus, schizophrenia is associated with an increased epsilon 4 allele frequency, as compared with controls (P = 0.01), that was indistinguishable from that found in either AD or Lewy body dementia. The increased epsilon 4 allele frequency was not associated with increased age of schizophrenia patient, indicating that it was not due to the coexistence of AD.